How To Treat Thrombocytopenia Naturally

Conquer Low Platelets

Alternative And Natural Therapies For Itp (idiopathic Thrombocytopenia Purpura). Live Free From Itp. Complete Program To Increase Platelets. This Is What You Will Learn With this Guide: The Two Herbs That can help bring up your platelets. The Two Vitamins needed to keep those platelets from dropping. What foods may cause your platelets to drop. How science has confirmed the benefits of these herbs in their use with low platelets. Why your doctor may not know about these natural alternatives and how you can assist him in helping you. Different tests that naturopathic doctors do to determine your real state of health that may reverse the course of your body drastically. Understand some of the reasons why people develop low platelets. Discover how your digestive tract may be the culprit to your low platelet level problems. How you can prevent the most drastic step a splenectomy. How you can restore your health so that you dont need any more dangerous drugs. Get your life back and stop ending up in the hospital all the time. Learn why your immune system is attacking your platelets and how to calm it down. Learn what over the counter medications to stay away from if you have low platelets Read more here...

Conquer Low Platelets Summary


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Autoimmune Thrombocytopenia

Thrombocytopenia is found in 25-40 of patients with APS, and is one of the most common presenting manifestations. Among these patients, thrombocytopenia is more frequently observed in patients with SLE than in patients with PAPS. aPL-related thrombocytopenia is a chronic, usually mild and is seldom associated with hemorrhagic complications. Bleeding may be related to several causes other than thrombocytopenia Autoimmune thrombocytopenia Autoimmune hemolytic anemia Microangiopathic hemolytic anemia Thrombotic thrombocytopenic purpura (TTP) high-intensity anticoagulation, hypoprothrombinemia (associ-tated with LA), and acquired defects of platelet function often associated with aPL. Values lower than 50 x 109 platelets L are uncommon, although platelet count can fluctuate with time. Severe thrombocytopenia is an additional risk factor for bleeding complications in these patients. Arterial and or venous thrombosis in APS may occur despite very low platelet count however, the frequency of...

Aciclovir And Other Antiherpes Drugs

A molecular relative ganciclovir, has antiviral activity against cyto-megalovirus (CMV) and is used to treat life-threatening CMV infections after bone marrow transplants, or CMV pneumonia or retinitis in AIDS patients. However, unlike aciclovir the drug induces rather severe neutropenia and thrombocytopenia. Although CMV does not have a viral TK enzyme,

Immunological Diseases

Wiskott-Aldrich syndrome is an X-linked disorder characterized by the triad of thrombocytopenia, recurrent infections and eczema. Patients have impairment of both humoral and cellular immune function. Increased serum IgE is frequently found. The distribution of the eczematous rash is different from that typically seen in AD and is less responsive to usual medical management.

Management options

Women should be delivered as soon as the maternal condition has been optimised, usually by Caesarean section. Recommendations vary regarding pre- or perioperative platelet transfusion, with some centres suggesting platelet transfusion if the platelet count is below 50 x 109 l and others not giving platelets until the count falls below 20 x 109 l. Regional anaesthesia is relatively contraindicated in the presence of thrombocy-topenia, but ultimately the anaesthetist must choose the anaesthetic technique which he or she judges to be the safest in the circumstance. The choice of regional anaesthesia in a woman with a platelet count of less than 80 x 109 l should be made only by an experienced consultant obstetric anaesthetist.

Obstetric Manifestations

It is impossible to predict which women will develop complications in pregnancy, and some women with persistently elevated aPL titers and a history of thromboses and or thrombocytopenia will have no obstetric complications at all. Previous poor pregnancy outcome remains the most important predictor of future risk.

Treatment of thromboembolism in pregnancy

Treatment of thromboembolism is with intravenous heparin initially (although subcutaneous low-molecular weight heparins (LMWHs) are increasingly used) and should not be delayed whilst awaiting investigation. Warfarin is associated with fetal abnormalities and in particular should be avoided in the first trimester and after 36 weeks' gestation. Acute treatment is followed by subcutaneous prophylactic heparin. It had been thought that prophylactic heparin caused stillbirth, prematurity and haemorrhage but more recent reviews controlling for maternal comorbidity have cast doubt on this assertion. Prophylaxis with LMWHs is now recommended because their use is associated with a lower incidence of osteoporosis and thrombocytopenia than unfractionated heparin, they require less monitoring, and they may be given as a once daily dosage. However, LMWHs have a prolonged action and are only partially reversible with protamine, meaning that LMWH prophylaxis may delay administration of regional...

Clinical features

Patients are mostly elderly adults although cases in younger individuals, including small children, have been reported 8,18-21,25 . There is a predominance of males. Clinically, they present with solitary (rarely), localized or, more commonly, generalized plaques and tumours with a characteristic 'bruise-like' violaceous aspect (Figs 16.1 & 16.2). Ulceration is uncommon. Mucosal regions may be involved (Fig. 16.3). The morphology of cutaneous lesions is similar to that of the skin manifestations of myelogenous leukaemia. In a distinct proportion of patients (approximately 30-40 ), skin lesions are accompanied by general symptoms and extracutaneous manifestations in the blood, bone marrow and or other organs. Lymph nodes are involved in approximately half of cases at presentation. Thrombocytopenia, anaemia and neutropenia are commonly found 2 .

Clinical Safety of Adenoviral Vector Products

Most of the completed and ongoing adenoviral vector clinical trials are early, uncontrolled trials. The absence of an internal control group limits the ability to draw definitive conclusions about the contribution of the adenovirus vector product to an adverse event. Despite this caveat regarding causality assessments, administration of replication defective adenovirus is associated with an acute cellular and cytokine mediated inflammatory response. Individuals have experienced systemic reactions such as fever, chills, hypotension, and laboratory findings consistent with disseminated intravascular coagulation, including thrombocytopenia. An overwhelming systemic inflammatory response, to which has been attributed, at least in part, the death of a volunteer in a trial of ornithine transcarbamylase (OTC) deficiency who received intrahepatic artery injection of a high dose of adenovirus-containing product, has not been observed in other clinical trials, including those that employ...

Ispinesib and related compounds

Cell Cycle Everolimus

For the combination of ispinesib and carboplatin, DLTs included prolonged (X5 days) grade 4 neutropenia, grade 4 thrombocytopenia, and grade 3 febrile neutropenia. The OTR was ispinesib at 18 mg m2 (the Phase II dose) and a car-boplatin target AUC of 6 (a commonly used monotherapy target exposure), both administered for q21 days. At the OTR, gastro intestinal (GI) toxicities were limited to grade 1 2 and minimal reports of grade 1 neuropathy were noted. The incidence of grade 3 4 thrombocytopenia and grade 3 4 neutropenia at the OTR were lower relative to full doses of carboplatin and ispinesib, respectively. At the OTR, is-pinesib concentrations did not appear to be affected by carboplatin and systemic exposures of carboplatin were within 11 of predicted values, suggesting no interaction with ispinesib. One patient with breast cancer had the best response of partial response at cycle 2. A total of 13 28 (46 ) patients had a best response of stable disease (duration 3-9 months) 15 .

Alcohol and substance abuse

Deficiency of thiamine leads to Wernicke's encephalopathy, polyneuropathy, and cardiac failure characterized by high cardiac output, low systemic vascular resistance, and loss of vasomotor tone. Folic acid deficiency causes bone-marrow depression and thrombocytopenia, leukopenia, and anemia. Special consideration must be given to the cardiovascular system of chronic alcohol users. Tachycardia, dysrhythmias, or cardiomegaly may indicate alcohol-related cardiac dysfunction and a 12-lead electrocardiogram (ECG) should be evaluated. Patients with alcohol-induced cardiac disease are less sensitive to endogenous or parenteral catecholamines. Hypokalemia and hypoglycemia are common, as are anemia, thrombocytopenia, and altered coagulation. These patients are often volume depleted and will require fluid resuscitation. Insert a urinary catheter to follow urine output. Intravascular monitoring should be individualized. Instrumentation of the esophagus should be avoided in patients with known...

Osteonecrosis Avascular Necrosis or Aseptic Necrosis

Asherson Syndrome

Asherson RA, Cervera R, de Groot PG, Erkan D, Boffa MC, Piette JC et al (2003) Catastrophic antiphospholipid syndrome international consensus statement on classification criteria and treatment guidelines. Lupus 12(7) 530-534 Asherson RA, Frances C, Iaccarino L, Khamashta MA, Malacarne F, Piette JC et al (2006) The antiphospholipid antibody syndrome diagnosis, skin manifestations and current therapy. Clin Exp Rheumatol 24(1 Suppl 40) S46-S51 Branch DW, Khamashta MA (2003) Antiphospholipid syndrome obstetric diagnosis, management and controversies. Obstet Gynecol 101(6) 1333-1344 Cabral AR, Cabiedes J, Alarcon-Segovia D (1990) Hemolytic anemia related to an IgM autoantibody to phosphatidylcholine that binds in vitro to stored and to bromelain-treated human eryth-rocytes. J Autoimmun 3(6) 773-787 Castanon C, Amigo MC, Banales JL, Nava A, Reyes PA (1995) Ocular vaso-occlusive disease in primary antiphospholipid syndrome. Ophthalmology 102 256-262 Cervera R, Khamashta MA, Font J, Reyes PA,...

Endotracheal or Tracheostomy Suction Specimens

For patients with pneumonia, a thin needle aspiration of material from the involved area of the lung may be performed percutaneously. If no material is withdrawn into the syringe after the first try, approximately 3 mL of sterile saline can be injected and then withdrawn into the syringe. Patients with emphysema, uremia, thrombocytopenia, or pulmonary hypertension may be at increased risk of complication (primarily pneumothorax air in the pleural space or bleeding) from this procedure, The specimens obtained are very small in volume, and protection from aeration is usually impossible. This technique is more frequently used in children than in adults.

Combination therapy with DNAdamaging agents

Arguably, the most clinically advanced PARPi is BSI-201 and this agent is currently being investigated in Phase III studies in TNBC as a combination with both gemcitabine and carboplatin 48 . The results of a randomized Phase II studies have been reported, where TNBC patients were treated with both gemcitabine and carboplatin and BSI-201 was given to one group of patients 49 . Interim results showed clinical benefit in 62 of patients on the BSI-201 combination, compared to 21 on chemotherapy alone. Improvements in survival were also noted, with median overall survival of 9.2 months compared with 5.7 months, respectively. The BSI-201 combination was well tolerated common severe side effects included neutropenia, thrombocytopenia, and anemia.

Turner Syndrome In Infants

Autobiography Turner Disorder

This infant has the thrombocytopenia-absent radius (TAR) syndrome. There is absence of the radius bilaterally. Note diat the absence of the radius of the right forearm has resulted in a club hand. In the TAR syndrome the thumb is always present. Figure 1.40. This infant has the thrombocytopenia-absent radius (TAR) syndrome. There is absence of the radius bilaterally. Note diat the absence of the radius of the right forearm has resulted in a club hand. In the TAR syndrome the thumb is always present. Figure 1.42. This infant has Fanconi's syndrome. Note the congenital absence of the right radius and right thumb. In Fanconi's syndrome the thumb may occasionally be present. Note the club hand with absence of the radius and the thumb. This may be unilateral or bilateral. In Fanconi's syndrome there is pancytopenia (anemia, neutropenia, and thrombocytopenia) in addition to the hypoplastic or absent thumbs and hypoplastic or absent radius. Figure 1.44. Another example of...

Fc Receptor Structure and the Design of Antiinflammatories New Therapeutics for Autoimmune Disease

Introduction - Inflammation caused by immune complexes in the blood vessels (vasculitis), the kidney (glomerulonephritis) and in the joints (arthritis) is a major cause of morbidity in autoimmune diseases. It is also one of the major mechanisms of tissue destruction in diseases including rheumatoid arthritis especially in the extra articular disease, immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE) and Wegner's granulomatosis. Whilst clear that in autoimmune diseases the likely initiation of the autoimmune process is a corruption of T cell regulation, the tissue damage and the perpetuation of disease are due to immune complexes. In the last decade, the role of Fc receptors as major initiators of inflammation caused by immune complexes has become more precisely defined with the use of recombinant Fc receptor (FcR) and gene knock-out or transgenic mice (1-8).

Symptoms And Signs

Transmission is commonly by droplet inhalation. Rarely, the transfusion of blood or blood products may lead to infection. At the peak of the viraemia, 1 week after exposure, there may be a mild flu-like illness with fever, chills and malaise, lasting 2-3 days. In many cases infection occurs without further symptoms. In erythema infectiosum the first sign is often marked erythema of the cheeks (slapped cheek appearance). A faint pink macular or maculopapular rash then develops on the trunk and limbs. As the rash fades a lacy or reticulate pattern may emerge. Recrudescence is common, especially after bathing or exposure to sunlight. In adult women symmetrical arthropathy is common (80 of cases), involving ankles, knees, wrists and fingers. This is normally resolved within 2-4 weeks. Low-grade fever may be present, and the rash may be pruritic. Leukopenia, reticulocytopenia and thrombocytopenia occur. Differential diagnosis. Other exanthems, especially rubella, also scarlet fever,...

Tcell And Combined Disorders

Primary disorders of T-cell function and combined T-cell defects come in many forms. One combined immunodeficiency, Wiskott-Aldrich syndrome (WAS), results from defects in the gene for the WAS protein (WASP), encoded on the X chromosome. WASP is a complex protein that functions in phagocytosis of microorganisms and apoptotic cells and regulation of cytoskeletal architecture in T-cells and platelets. WAS results in to profound humoral and cellular deficiency hallmarked by eczema, excessive bleeding, and thrombocytopenia. Patients usually have elevated levels of IgE and IgA accompanied by low levels of IgM. Atopic dermatitis and recurrent infections, including otitis media, pneumonia, sinusitis, meningitis, or sepsis, with pneumococci or other encapsulated bacteria present during the first 12 mo. BMT from HLA-identical siblings or HLA-matched unrelated donors have resulted in complete correction of both platelet and immunological abnormalities. in the intracellular domain of the Fas...

Application of Linkage to SLE

Thrombocytopenia And Genetic

As discussed, SLE is a complex autoimmune disease with a definite genetic predisposition. However, the exploration of SLE genetics is in its infancy. SLE is an extremely complicated clinical illness with a wide range of manifestations. Clinical manifestations of SLE can be very diverse, with glomerulonephritis, dermatitis, thrombosis, vasculitis, seizures, arthritis, hemolytic anemia, and thrombocytopenia counted among the disease's manifestations. Consequently, the variation between patients is incredible. Indeed, it is possible to have two patients afflicted with SLE who satisfy the classification criteria three different ways with no features in common. This degree of clinical heterogeneity may be because of the involvement of multiple major and modifier genes. Thus far, the genome scans have been performed using a general SLE phenotype. Second, we have used an ad hoc correction designed to maintain the overall genomewide significance level (5 level) to detect the significant...

What is HELLP syndrome

HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) is a complication of preeclampsia. Patients develop a microangiopathic hemolytic anemia associated with thrombocytopenia and elevated liver enzymes. Ten to twenty percent of these patients will have normal blood pressure, making the diagnosis sometimes difficult. Although HELLP syndrome is not an indication itself for immediate cesarean delivery, delivery is the only definite treatment for preeclampsia. Patients who develop laboratory evidence of disseminated intravascular coagulation are delivered immediately, regardless of gestational age.

What constitutes the basic laboratory evaluation of coagulation status

Chapter 7 reviews physical and historical information that might suggest disruption in coagulation. The basic laboratory evaluation includes platelet count, bleeding time, prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time. The minimal number of normally functioning platelets to prevent surgical bleeding is 50,000 mm3. It is important to note that both the PT and PTT require about a 60 to 80 loss of coagulation activity before becoming abnormal, but patients with smaller decreases in function can still have significant surgical bleeding. Therefore the history is still very important. Thromboelastography measures the combined function of platelets and coagulation factors.

What are the reported benefits and adverse effects of fish oil

Fish oils are used primarily in the treatment of hyperlipidemia, hypertension, and chronic inflammatory states such as rheumatoid arthritis and autoimmune disease. Fish oils contain two long-chain omega-3 fatty acids that compete with arachidonic acid in the cyclooxygenase and lipoxygenase pathways and have antiinflammatory effects, likely caused by the inhibition of leukotriene synthesis. Fish oils decrease blood viscosity and increase red blood cell deformability. The antithrombotic activity offish oils results from prostacyclin inhibition, vasodilation, reduction in platelet count and adhesiveness, and prolongation of bleeding time. Concomitant use of fish oils and anticoagulant and antiplatelet drugs previously mentioned may increase the risk of bleeding.

What are the anesthetic considerations in patients with preeclampsia

Before initiation of neuraxial anesthesia, evaluation of coagulation status is recommended. Because thrombocytopenia is the most common coagulopathy in preeclampsia, a screening platelet count is recommended. Although an arbitrary platelet count of 100,000 is often suggested, the actual platelet count safe for spinal or epidural placement is unknown.

Since these medications appear to impair coagulation how can their effect be evaluated clinically

The best means for detecting a coagulation defect secondary to herbal medications is a properly taken clinical history. Especially important are questions related to the hemostatic response during previous surgeries. Also important are questions regarding bleeding tendencies such as easy bruising, gingival bleeding, or excessive bleeding following procedures such as dental extractions. Positive responses suggest the need for laboratory testing. The most commonly used measures of coagulation include the activated partial thromboplastin time, which evaluates the intrinsic system, the prothrombin time, which evaluates the extrinsic pathway, platelet count, and bleeding time. However, bleeding time, the most commonly used measure of platelet function, is subject to many variables and may not always be reliable. More reliable tests of platelet function are available but are expensive, time-consuming, and not appropriate for routine screening.

Relative contraindications

Syndrome), hepatic disease may be overshadowed by the severity of the comorbid conditions. Prior abdominal surgeries and encephalopathy are important features to note, as are coagulation deficits (factor deficiencies and thrombocytopenia). The thromboelastogram (TEG) provides valuable insight into the patient's entire clotting process. The TEG graphs the viscoelastic properties of a clot from the formation of the first fibrin strands to the full hemostatic plug. Thus the TEG is a dynamic test showing the evolution of clot formation. Because the TEG examines multiple phases of clot formation within a single test, it reflects information that is otherwise available only in multiple tests. The TEG is the best laboratory assessment of qualitative platelet function.

Outline the initial management of an unconscious hypotensive patient

The ABCs (airway, breathing, and circulation) are essential. Unconscious patients require rapid and definitive airway control. The trachea should be intubated in a rapid-sequence fashion. Establish numerous large-gauge sites of intravenous access, using either short 14-or 16-G catheters peripherally or 9 Fr introducers into the central circulation. Quickly bolus the patient with at least 2 L of balanced crystalloid solution. Failure to respond indicates a need for blood. If crossmatched blood is unavailable, transfuse O-negative or type-specific red blood cells. If more than 2 units of O-negative red bloods cells is given, continue administering O-negative blood. Establish an arterial catheter for continuous monitoring and blood analysis (arterial blood gases, hematocrit, platelet count, coagulation profiles, and blood chemistries).

Rationale For Selective Targeting Of Jak3 In Inflammatory Diseases

These observations make it difficult to assess the risk to benefit ratio of dual inhibition of JAK1 and JAK3 a priori. JAK2 is classically associated with interferon- (IFN-g) production through the IL-12 pathway however, it also mediates the signaling of important hematopoietic growth factors such as erythropoietin (EPO), thrombopoietin (TPO) and granulocyte macrophage colony-stimulating factor (GM-CSF). As a result, JAK2 inhibitors are being examined for oncological applications, and this is beyond the scope of this review. It has been suggested that JAK2 inhibition may result in adverse hematopoietic effects such as anemia, thrombocytopenia and generalized leukopenia in the clinic 12 .

Differential Diagnosis

On the other hand, it may be very difficult to differentiate APS from MS, since neurological manifestations and MRI can be indistinguishable. Both conditions can show oligoclonal bands in the CSF. Clues in those cases include a past history of venous thrombosis and pregnancy loss, suggesting APS, and the presence of atypical features of MS such as migraine or epilepsy, or other features such as livedo reticularis, sicca syndrome, Raynaud's, SLE features, or thrombocytopenia. Catastrophic APS has a number of clinical similarities to heparin-induced thrombocytopenia. In the latter, patients develop thrombosis at any site, both arterial, venous and microvascular (especially the skin). It usually develops within 10-14 days after starting heparin, and the first sign is a falling platelet count. aPL screen may also be indicated in other situations such as thrombocytopenia, livedo reticularis, low levels of free prot-S (unknown mechanism), prot-C, and factor XII, and the presence of...

Sources of Complexity and Clinical Heterogeneity in SLE

In general, SLE may range from not much more than a nuisance to an immediately life-threatening illness. Mortality in SLE is associated with several disease features, including thrombocytopenia most prominently (15,16). Nonetheless, prediction of severity of disease or mortality in an individual remains virtually impossible. Thus, the disease has marked heterogeneity regarding its severity as assessed by mortality.

Treatment of Anemia in Elderly Patients with CKD

Given the limited data available, elderly patients with CKD, whether on dialysis or not, should probably be evaluated and treated for their anemia as generally recommended for patients with CKD regardless of age (5). The most recent clinical practice guidelines and recommendations for the National Kidney Foundation KDOQI for Anemia in CKD recommend that Hgb testing be carried out at least annually in all patients with CKD, regardless of stage or cause, and that a diagnosis of anemia should be made and evaluation should be undertaken when the Hgb level is less than 13.5 g dL in adult males and 12.0 g dL in adult females. This evaluation should include a complete blood count (CBC), red blood cell indices (mean corpuscular hemoglobin MCH , mean corpuscular volume MCV , mean corpuscular hemoglobin concentration MCHC ), white blood cell count, and differential and platelet count, absolute reticulocyte count, serum ferritin to assess iron stores, and serum TSAT or content of Hb in...

Classification Criteria for APS

An international consensus statement on classification criteria for definite APS was published in 1999. A patient with APS must meet at least one of the two clinical criteria (vascular thrombosis or pregnancy complications) and at least one of the two laboratory criteria (aCL and or LA). Although these criteria have been shown to be specific and sensitive for the classification of primary and secondary APS, the absence of major or essential features in the presence of minor features should not discourage the clinician from making the diagnosis when other causes of such features have been ruled out, since other well-recognized features of APS such as thrombocytopenia, hemolytic anemia, transient ischemic attacks, transverse myelitis, livedo reticularis, valvular heart disease, demyeli-nating syndromes, chorea, and migraine were not thought to have as strong an association as the final criteria and were excluded as classification criteria. These criteria have been revised in 2006 to...

Everolimus Immunosuppressant [4346

Everolimus, an oral immunosuppressant for the treatment of kidney and heart transplant rejection, is the 40-0-(2-hydroxyethyl) derivative of rapamycin. It has immunosuppressive properties similar to those of rapamycin, but with improved pharmacokinetic profile. In addition, the 40-0-(2-hydroxyethyl) group alters the physico-chemical properties of the macrolide to allow galenic formulation. Everolimus is prepared in a two-step semisynthesis starting from rapamycin, by alkylation of the 40-hydroxyl group with t-butyldimethylsilyloxyethyl triflate and subsequent cleavage of the silyl protecting group. Everolimus, like rapamycin, is a proliferation signal inhibitor that exerts its immunosuppressive effect by inhibiting the activation of p70 S6 kinase, thereby blocking growth factor-driven proliferation of T cells, B cells and vascular smooth muscle cells, and arresting cell cycle at the G1 phase. Inhibition of p70 S6 kinase activation by everolimus and rapamycin is mediated by their...

Formulary And Economic Considerations

There are four general types of pharmacoeconomic analyses that are used to help determine the possible value of any given therapy. The first type, cost minimization analysis, is the most common type reported in the medical literature. This analysis is used to compare the costs associated with competing therapies and does not consider outcomes or benefits. In fact, it usually presumes that outcomes are equivalent. For example, antibacterial X costs 1,000 for a course of therapy compared with 500 for therapy Y, so therapy Y is the preferred approach because it is less costly. What if therapy X decreased the length of hospital stay or time on mechanical ventilation compared with therapy Y in patients with ventilator-associated pneumonia In this case, the savings associated with therapy X could be large, considering that the development of ventilator-associated pneumonia has been shown to increase mean hospital charges per patient by more than 40,000 (45). What if therapy Y causes...

Prophylaxis and Treatment

Once ATRA syndrome has developed, addition of low-dose CT is ineffective in lowering WBC counts, and leukapheresis is unable to reverse symptoms. Two different approaches aimed at preventing or treating early ATRA syndrome are proposed. One of them, mainly used by the European and Japanese groups 33, 37,109 , consists of adding CT from the onset of ATRA in patients presenting with high WBC counts (WBC greater than 5,000 mm3 in the European trial, or greater than 3,000 mm3 in the Japanese trials) or when increases in the WBC counts are seen with ATRA. This approach has been associated with a low incidence of fatal ATRA syndrome. A disadvantage of this approach is that about two-thirds of the patients treated with ATRA also received early CT. However, several reports have shown that the period of neutropenia and thrombocytopenia is significantly shorter in patients who receive CT while already on ATRA, by comparison with CT alone 37, 115 . Furthermore, intensive CT, if not administered...

Stealth warfare The interactions of EPEC and EHEC with host cells

EHEC usually refers to serotype O157 H7 and less commonly to serotype O111 H-. An EHEC infection is often heralded by the onset of watery diarrhea, which progresses rapidly to severe bloody diarrhea (hemorrhagic colitis) in many patients, regardless of age (Nataro and Kaper, 1998). In the very young and very old, as well as in immunocompromised patients, the disease can be complicated by the onset of hemolytic-uremic syndrome (HUS), which is characterized by hemolytic anemia, thrombocytopenia, and renal failure. HUS is caused by the secretion by EHEC of shiga-like toxin (SLT), a potent cytotoxin with a predilection for human kidney cells. A description of the mechanisms of action of SLT and the many effects on the host cell is beyond the scope of this chapter but is reviewed by O'Loughlin and Robins-Browne, 2001. The onset of HUS, even with rapid treatment, can prove fatal to a patient. Outbreaks of EHEC infection are becoming increasingly high profile in North America and Europe. The...

Anaplasma phagocytophilum

Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium of the order Rickettsiales (Goodman et al. 1996 Dumler and Bakken 1998 Demma et al. 2005). It is the causative agent of tick-borne fever (TBF), an emerging zoono-sis in the United States and in other regions of the world. This infection is characterized by fever, headache, myalgias, thrombocytopenia, and leukopenia. The principal reservoirs are sheep, cattle, and goats. In humans, this pathogen causes granulocytic anaplasmosis. Bacterial invasion of neutrophil granulocytes is the hallmark of the disease, but other cells such as endothelial cells are also infected by this pathogen (Goodman et al. 1996 Munderloh et al. 2004 Herron et al. 2005).

Cryoablation and Radiofrequency Ablation

Tumors adjacent to the major vascular channels (portal or hepatic vein or IVC) may not be reliably ablated because the blood flow acts as a thermal sink, protecting the malignant cells on the vessel wall from the applied temperature extremes. The great advantage of these techniques is that they can destroy tumor in disparate parts of the liver and preserve intervening parenchyma. They are, therefore, ideally suited to smaller tumors. Indeed, the larger the amount of dead (frozen or coagulated) left in the liver, the more likely are adverse systemic consequences. These adverse consequences are a variant of a systemic inflammatory response and include thrombocytopenia, myoglobinuria, ATN, and noncardiogenic pulmonary edema. They are increasingly prevalent as the volume of ablated tissue passes 30 of the liver volume, and appear to be more prevalent following cryoabalation than following RFA (6).

Syk kinase inhibitors which have progressed to clinical studies

An orally bioavailable prodrug of 4 is currently in clinical trials for treatment of RA and immune thrombocytopenia purpura 33,34,66 . This compound potently inhibited all Syk-dependent cell-based assays, including Fc receptor signaling in human macrophages, neutrophils, mast cells and B-cell receptor signaling in human B cells. Selectivity was demonstrated by the examination of inhibition of phosphorylation in cells, and with a panel of off-target Syk-independent cell-based assays. Inhibition of Flt3, Jak and Lck, was also observed, which for inflammatory processes might be considered to be favorable 34 . Animal models were conducted that could be directly correlated to IC-mediated inflammatory processes proven to be dependent on activating Fcg receptors 33-35 . Such models included the passive Arthus reaction and passive anticollagen type II antibody-induced arthritis (CAIA) models 33-35 . Based on the compound's biological potency, selectivity, PK characteristics, safety and...

Therapy And Prophylaxis

Since more than 95 of the IM patients recover without specific therapy, and specific therapy does not show significant clinical benefit, the treatment is usually symptomatic. The duration of fever is reduced to 2 to 5 days using prednisolone (40mg day decreased to 5mg day by the 12th day). However, this treatment has gained no general acceptance because of the fear of inducing myocarditis or meningoencephalitis. Corticosteroids may be used in airway obstruction, severe thrombocytopenia, haemolytic anaemia or selected cases of prolonged prostration. Some also use similarly administered corticoids in involvement of the central nervous system, myocarditis, or pericarditis, starting at a higher dose (prednisone, 60-80 mg day). Metronidazole has been claimed to reduce the pharyngeal symptoms, but neither this drug nor chloroquine, which has also been tried, showed any significant effect on general health. In randomized trials aciclovir showed no significant clinical effect. Oropharyngeal...

Toxicity of Intravenously Administered ARCAs in the Absence or Presence of Docetaxel

A synergistic antitumor efficacy was observed when CV787 was combined with taxane in the prostate tumor xenograft 88 . To examine the toxicity of CV787 in combination with the chemotherapeutic agent docetaxel, we conducted a fourth toxicology study in C57BL 6. The 4-day and 2 8-day effects were evaluated in mice given a single daily dose of dexamethasone (Decadron) each day for 3 consecutive days, a single injection of CV787 at low (1 x 108 particles per animal), medium (3 x 109 particle per animal), or high (1 x 1011 particles per animal) dose, and a single dose of the chemotherapeutic agent, docetaxel (100 mg m2). Six different treatment groups were established using identical treatment regimens for animals in subgroups sacrificed at 4 days and at 28 days. Each treatment subgroup consisted of eight randomly assigned mice. The ARCA virus vehicle and all three doses of virus were given intravenously via tail vein injection. All virus injections were given on day 1 at 1-2 h prior to...

R406R788 fostamatinib

In an ascending dose Phase IIa study (TASKi1), R788 achieved a significant and dose-related clinical response, with 72 of patients in the 150 mg bid group achieving ACR20 response compared to 38 on placebo 73 . This efficacy correlated with a reduction in IL-6 and MMP-3 levels. In a Phase IIb trial (TASKi2) in methotrexate failures, R788 showed clinical improvement after 1 week and sustained efficacy thereafter, with 43 of patients achieving ACR50 response (placebo 19 ) after 6 months of dosing at 100 mg bid 74 . In the subsequent TASKi3 trial, however, ACR scores for R788 were not significantly different from placebo, although MRI scans did show improvements in synovitis and osteitis. The most common adverse effects were diarrhea, hypertension, and neutropenia. In a Phase II trial for refractory ITP, R788 increased and maintained platelet count in 50 of patients. Efficacy increased with dose, as did gastrointestinal adverse events 75 . It is unclear if off-target effects may...

Myelodysplastic Syndromes and Aplastic Anemia Pathologic and Immunologic Implications

The Myelodysplastic Syndromes (MDS) represent a heterogeneous group of bone marrow diseases of uncertain etiology characterized by a variable degree of cytopenias, predominantly but not exclusively anemia that is often macrocytic (1). The cytopenias reflect both ineffective hematopoiesis (marrow dysplasia or accelerated apoptosis) and increase in marrow leukemic blasts (2). In 85 of cases the marrow is normo to hypercellular but in 15 the marrow cellularity can be below 30 and, on occasion, below 15 , which raises the differential diagnosis with acquired aplastic anemia (3). In such instances it is necessary to depend on the morphologic identification of significant dysplasia of one or more of the myeloid cell lines or the identification of small clusters of blasts on a bone marrow biopsy. Over 50 of all cases occur in patients over the age of 70 years. Each year some 15,000 individuals will be diagnosed with MDS, although this may well be an underestimate. In a recent national survey...

Etiologic Factors For Intracerebral Hemorrhage

An ICH, classified as either primary or secondary, can be caused by a variety of factors (Table 1). Primary ICH refers to spontaneous hemorrhage from systemic hypertension. Hypertensive ICH usually occurs in middle-aged to older patients, and the hemorrhage might be attributed to small aneurysmal dilatations on the small, perforating cerebral arteries. These aneurysms are usually multiple, tend to occur in arteries

Preoperative Testing And Preparation

Horse Brain Anatomy

Cirrhotics, atrophy of the right lobe, hypertrophy of the left lobe, and hypertrophy of the caudate lobe are all common, and can require alteration of the plan of attack. Endoscopy is very desirable preoperatively in cases done for upper gastrointestinal bleeding. Although common, varices are not the only possible reason for upper gastrointestinal bleeding in alcoholic patients. TIPS has no beneficial effect on common nonvariceal causes of bleeding such as Mallory-Weiss tears or gastritis. Blood tests include LFTs, BUN, and Creatinine determination, PT PTT, hemoglobin, hematocrit, and platelet count. Hydration of the patient is desirable, particularly in those with any degree of renal insufficiency. Radiographic contrast presents a special risk to those patients. Prophylactic antibiotics are generally given to patients preoperatively. Many regimens exist. Correction of coagulapathy is sometimes desirable, but fairly controversial. So many of these patients have baseline coagulopathies...

Acquired thrombophilia

Of women with recurrent miscarriage (three or more), 15 have persistently positive results for phospholipid antibodies. If untreated, 90 will have spontaneous abortions or stillbirths in subsequent pregnancies. It is possible that lupus anticoagulant (30 of cases) and anticardiolipin antibodies (70 of cases) are the same autoantibody identified in different assays. Clinical features of the antiphospholipid syndrome are recurrent fetal loss, thrombosis (arterial and venous), thrombocytopenia, haemolytic anaemia, hypertension, pulmonary hypertension and livedo reticularis. Antiphospholipid syndrome is associated with a 5 incidence of thromboembolism or cerebrovascular accident in pregnancy.

Laboratory Evaluation

Laboratory measurements that should raise concern for portal hypertension include abnormal liver chemistries and other serum markers of chronic liver disease. Elevated aminotransferases signal hepatocellular injury, but there is no correlation between the degree of transaminase elevation and the severity of histologic injury. Cholestatic liver chemistries (increased alkaline phosphatase, GGT) may reflect chronic biliary obstruction from PBC or PSC. Hypoalbuminemia and elevated prothrombin time suggest possible decreased hepatic synthetic function. Thrombocytopenia is commonly found in patients with portal hypertension, splenomegaly, and platelet sequestration. An abdominal ultrasound examination that demonstrates a large-diameter portal vein in combination with a platelet count of 140,000 mm3 or less is a sensitive predictor of portal hypertension (5).


Right heart failure is an absolute contraindication to TIPS, as these patients respond badly to arrival of high-volume portal venous flow directly into their compromised right hearts. Fatal cases of congestive heart failure have occurred. Severe hepatic encephalopa-thy or liver failure is a relative contraindication to TIPS, as the shunt decreases intrahe-patic portal venous flow in most patients, potentially diminishing already compromised function. That being said, TIPS is often performed in this patient population on a nothing to lose basis, as it is sometimes the only available therapy for a severely encephalopathic patient who is also bleeding. Whereas untreatable encephalopathy, liver failure, and death sometimes do result, many patients do surprisingly well, and seemingly unsalvageable patients can sometimes be salvaged. Severe coagulopathy caused by liver dysfunction is unfortunately common in this patient population, but is only a relative contraindication to TIPS. The...

Treatment of Chronic HCV Infection with IFNa

Ribavirin is administered at a dose of 0.8-1.2 g day, depending on body weight and the HCV genotype (2002). Higher doses may be necessary for heavy patients. The addition of ribavirin increased the SVR rate to 41 and 43 , respectively, compared to 16 and 19 with standard IFN-a2a and IFN-a2b monotherapy (McHutchison et al. 1998 Poynard et al. 1998). In the three main registration trials (randomized controlled studies involving patients without cirrhosis), pegylated IFN-a plus ribavirin gave global SVR rates of 54-56 , compared to 18-39 with pegylated IFN-a monotherapy (Fried et al. 2002 Hadziyannis et al. 2004 Manns et al. 2001). The SVR rates ranged from 76 to 84 in patients with HCV genotype 2 or 3 infection and from 42 to 52 in patients with HCV genotype 1 infection. Little information is available on patients with other genotypes, but the SVR rates in patients with HCV genotype 4 infection appear to be close to those in patients with genotype 1 infection. Pretreatment variables...

Problemsspecial considerations Preexisting disease

In terms of general anaesthetic management, the problems of pre-existing renal disease are the same as in the non-pregnant population. These include the underlying cause of renal impairment, systemic manifestations of renal failure (in particular, hypertension and ischaemic heart disease, thrombocytopenia and anaemia), the patient's medication, altered handling of drugs and fluid management, including the nature and timing of dialysis.

What are the gastrointestinal and hematologic derangements that occur with cirrhosis

Hematologic disorders include anemia, thrombocytopenia and coagulopathy. Anemia is secondary to GI bleeding, malnutrition, and bone marrow suppression. Thrombocytopenia is caused by splenic sequestration, bone marrow depression, and immune-mediated destruction. Coagulopathy is caused by decreased synthesis of clotting factors, accelerated fibrinolysis, and disseminated intravascular coagulation.


The antiphospholipid syndrome (APS), first described in 1983 by Dr. Graham Hughes and his team at the Hammersmith Hospital, included recurrent arterial and venous thromboses, fetal losses, and thrombocytopenia in the presence of autoan-tibodies, the so-called antiphospholipid antibodies (aPL). Although a wide variety of clinical manifestations have been added over the last 5 years, these major features have stood the test of time. Many patients with APS have clinical and laboratory features common to other autoimmune diseases, particularly systemic lupus erythematosus (SLE). Such patients are defined as having secondary APS to distinguish them from patients with features of APS alone (primary APS-PAPS). There appears to be very few differences, if any, between the clinical complications associated with the primary and the secondary form of the syndrome, and the rates of arterial or venous thrombosis or fetal loss do not appear to be different. Distinguishing between PAPS and APS due...

Laboratory Findings

Blood and peritoneal fluid cultures will yield organisms of enteric origin in about one-fourth of patients. Yeast may be isolated from peritoneal fluid, especially in infants who had been treated with antimicrobials. In the event of an outbreak in a nursery, it is important to evaluate both cases and matched concurrent controls. Viruses can be detected antigenically or through genetic methods. In some infants, the white blood count may be very low or very high and the platelet count usually will be diminished and falling rapidly. At least 50 of infants with NEC have platelet counts of 50,000 per millimeter or less (45). Prothrombin and partial thromboplastin times are elevated. Hyponatremia is common at the outset of NEC.

Platelet Pathology

Large Platelets and Thrombocytopenia 3.1.1. Bernard-Soulier Syndrome autosomal recessive genetic disorder is characterized by the presence of abnormally large platelets seen on peripheral blood smears, mild thrombocytopenia, and prolonged bleeding time. The hallmark of BSS is a defect or congenital deficiency of the platelet glycoprotein Ib V IX complex (GPIb V IX). GPIb is the receptor for von Willebrand factor (vWF) whereby platelets adhere to the exposed vascular endothelium, and also binds thrombin (2, 21-23). The severity of thrombocytopenia in BSS is variable, with platelet counts ranging from less than 30 to as much as 200 x 103 L (

Adjunctive Therapy

Argatroban, lepirudin, and bivalirudin are all direct thrombin inhibitors. These agents should replace heparin in cases in which the diagnosis of heparin-induced thrombocytopenia (HIT) type II is confirmed or even suspected. HIT type II is an immune-mediated disorder characterized by the formation of antibodies against the heparin-platelet factor 4 complex, resulting in thrombocytopenia, platelet aggregation, and the potential for arterial and venous thrombosis. The possibility of HIT type II should be raised in patients who demonstrate a platelet count drop to less than 100,000, or by greater than 50 from baseline, in the setting of heparin therapy (usually 5-12 days after initial exposure). Unexplained thrombotic events should also evoke this diagnosis, even in the setting of a normal platelet count. Impaired renal function must be taken into account when selecting the appropriate agent argatroban is the only direct thrombin inhibitor that is hepatically cleared.


In Vivo Efficacy - FcyRlla is absent in mice and receptor antagonists cannot be tested in inbred strains of mice. A transgenic mouse expressing FcyRlla could be used for in vivo evaluation of receptor antagonists. The collagen-induced arthritis model (CIA) is used as an in vivo model for evaluating anti-arthritic drugs (33). Even though the strain of transgenic mice is on a resistant H-2b haplotype, these mice develop CIA with similar features of the disease to the DBA 1 strain. As the transgenic mice also express FcyRlla on platelets (as in humans), the same mice can be used to test the efficacy of the inhibitors against immune thrombocytopenia.

Analgesia for labour

Regional analgesia is the method of choice. Good analgesia prevents hypertensive episodes associated with contraction pain. Well-conducted epidural or combined epidural-spinal analgesia may be beneficial to the compromised fetus by improving uteroplacental perfusion. A combination of low-dose local anaesthetic and opioid may be given by continuous epidural infusion or intermittent boluses, and this can be supplemented as necessary should instrumental or operative delivery be required. A pre-epidural platelet count should be performed (if trends suggest that platelet numbers are decreasing significantly, a platelet count should be repeated immediately before epidural injection is commenced). Current opinion suggest that a platelet count of at least 80 x 109 l is advisable before instituting central neural blockade, although any stated lower safe limit is entirely arbitrary, and the relative risks and benefits of regional analgesia and anaesthesia must be considered for each patient....

Autoimmune disorders

Several autoimmune responses result in the generation of autoantibodies, which can promote cell and tissue destruction and chronic inflammatory responses via Fc receptor activation on leukocytes 17 . Autoantibodies against antigens on the cell surface of blood cells, for example, can result in the rapid destruction of these cells by macrophages localized in the reticuloendothelial system of the spleen and liver. Immune thrombocytopenia purpura (ITP) and autoimmune hemolytic anemia (AIHA) are caused in large part by self-reactive antibodies against platelet antigens (e.g., GPIIb-IIIa, GPIb-IX, GPIb, GPIIIa) and erythrocyte antigens (e.g., Band 3) 30 . Experimental mouse models of ITP and AIHA are dependent on FcgR-signaling, which in turn depends on Syk kinase activity for activation of phagocytes. Indeed, treatment with a Syk kinase inhibitor reduces platelet loss in an experimental murine model of ITP 31 .


Should include detailed medical and obstetric history, documentation or confirmation of significant levels of aPL, review of medication, information of maternal and obstetric problems' risk and information of possible further treatments, blood tests (renal, blood cell count, liver, urine, ). In those who have systemic lupus erythematosus (SLE), issues related to exacerbation of SLE also should be discussed. All patients should be assessed for evidence of anemia and thrombocytopenia, which occur in association with APS. The potential complications of heparin treatment during pregnancy includes hemorrhage, osteoporosis, fracture, and hep-arin-induced thrombocytopenia. The reported rate of osteoporosis and associated fracture is low, though cases have occurred. Whether LMWH during pregnancy is associated with decrease of bone density remains controversial. Calcium and vitamin D supplements may be added during this treatment. Heparin-induced thrombocytopenia...


There have been few published cases of polycythaemia complicating pregnancy. There may be associated thrombocytopenia or thrombocythaemia. Thrombocytopenia may be dilutional and may not reflect function. Thrombotic events (arterial and venous) do occur and prophylactic aspirin and heparin have been given to prevent them.

Vasospasm After aSAH

Papaverine is the only FDA-approved intra-arterial vasodilator. It is short lived but not without risk. Reported complications include rapid increases in intracranial pressure (which typically return to normal with discontinuance of papaverine infusion) (101), transient neurologic deficits (including mydriasis) (102), brain stem depression (103,104), monocular blindness (105), seizures (105,106), thrombocytopenia (107), precipitation of embolic crystals (108), and paradoxic exacerbation of vasospasm that leads to cerebral infarction (109). In fact, at higher concentrations, papaverine can precipitate in blood, which can also be embolic.


Although gastrointestinal symptoms are the most common reported toxicity, reversible myelosuppression (thrombocytopenia, leukopenia, and or anemia) has been the most important treatment-limiting side effect, with higher rates observed than the original registration studies. Bone marrow examination has shown changes similar to those observed with reversible chloramphenicol toxicity (98,99). Such toxicity is usually observed only with linezolid treatment that exceeds 2 weeks. Other reported toxicities of note include gastrointestinal upset, rare cases of serotonin syndrome, optic and peripheral neuropathy, and lactic acidosis (100-103).


Cocaine, or its water-insoluble derivative crack, causes central and peripheral dopa-minergic and adrenergic stimulation resulting in euphoria, increased alertness, vasoconstriction and hypertension. Myocardial ischaemia and arrhythmias may occur, and convulsions, intracranial haemorrhages and renal, hepatic and haematological impairment (including thrombocytopenia) have been reported. Cocaine abuse has been associated with increased incidence of spontaneous abortion, placental abruption, premature labour and fetal morbidity and mortality. Prolonged action of suxamethonium has also been reported. Diagnosis may be difficult since its use is often denied and the presentation may resemble that of pre-eclampsia and phaeochromocytoma. Urine remains positive for cocaine metabolites up to 3 days after use, and testing has been suggested in all at-risk groups (e.g. known users of other drugs, unbooked pregnancies, etc.).


In March 1990, a 42-year-old man known to be an episodic heavy drinker and regular smoker suddenly developed a right visual field defect caused by a left occipital brain infarct. A few weeks prior to the index stroke he had an anteroseptal and inferior myocardial infarct, and after discharge from hospital, he had started to drink large amounts of alcohol daily. In April 1995, he developed a right occipital brain infarct. This 'accident' was again preceded by a drinking bout of about two weeks (900 g ethanol per week). On admission, clinical examination showed tubular vision. A computed tomography head scan revealed two separate infarcts located on the left and right occipital lobes. Duplex imaging of the carotid and vertebral arteries showed neither occlusions nor significant stenoses, but transthoracic echocardiography (TTE) showed left ventricular inferior and anteroapical hypokinetic segments without any thrombi. Three days after the onset of the latter stroke, the patient's...


Pre-eclampsia encompasses HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome, eclampsia and possibly acute fatty liver of pregnancy. Although the disease is progressive, a mother may be asymptomatic until she presents with an eclamptic fit, and although pre-eclampsia is a disease of pregnancy, terminated only by delivery, pre-eclampsia, HELLP syndrome and eclampsia may all present only after delivery.


The use of corticosteroids in APS pregnancies is rare except for the treatment of maternal thrombocytopenia or co-existent SLE, for which prednisolone is still first line therapy. Regular blood glucose monitoring is required with long-term administration of steroids. Patients requiring 7.5 mg prednisolone daily for more than 2 weeks prior to delivery should be given intrapartum intravenous hydrocortisone 100 mg tds. Breast feeding is rarely contraindicated, although women taking 60 mg prednisolone with healthy term babies may consider bottle-feeding because of the theoretical risk of neonatal hypo-thalamic-pituitary adrenal suppression at these high doses.

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