Thrombocytopenia Ebook

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 More here...

Conquer Low Platelets Summary

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Animal Toxicology Studies

In an effort to more closely simulate the clinical situation in which abciximab likely would be applied, monkeys were treated with a bolus dose of 0.3 mg kg, followed by a continuous 48-hour infusion at 0.45 or 0.5 mg kg min, in combination with aspirin, heparin and either tPA or streptokinase. This study confirmed that pairing an abciximab bolus and infusion with standard antiplatelet, antithrombotic, and fibrinolytic therapy was well tolerated both acutely and for at least 3 weeks following treatment. The combination regimen was not associated with any signs of acute adverse reactions, such as hypersensitivity, hemorrhage, or thrombocytopenia.

Proliferation and Cell Cycle Progression

Originating from a gene duplication, the two paralogs HDAC1 and HDAC2 are often found in the same multiprotein complexes and share 82 identity on the amino acid level suggesting a certain redundancy in their functions. However, in the developing mouse embryo HDAC1 and HDAC2 cannot compensate for each other, indicating some nonredundant roles during early development. A remarkable example of specific roles for HDAC1 and HDAC2 is the developing brain, where these two enzymes exhibit different developmental stage- and lineage-specific expression patterns (MacDonald and Roskams 2008). However, mice lacking HDAC1 or HDAC2 in neuronal precursors exhibit no overt neurological phenotype (Montgomery et al. 2009). Also in other differentiated cell types such as fibroblasts, B cells, hematopoietic cells, and cardiomyocytes, HDAC1 and HDAC2 have partially redundant functions, as there are no strong phenotypes for ablation of individual genes observed (Montgomery et al. 2007 Wilting et al. 2010...

Clinical Trial Findings

Filgrastim alone or in combination with chemotherapy is an effective agent for recruiting peripheral blood progenitor cells with long-term reconstituting ability (60-66). In a historically controlled study, Filgrastim-generated PBPC in conjunction with autologous BMT and Filgrastim accelerated recovery of neutrophil and platelet count (62). Use of Filgrastim for mobilisation resulted in a significantly accelerated time to recovery of granulocytes when compared with non-mobilised PBPC recipients in a study of 85 patients with relapsed HD (60). The use of mobilised PBPC resulted in a significantly accelerated time to platelet engraftment when compared with non-mobilised PBPC recipients. There was a statistically significant reduction of costs in patients who received Filgrastim-mobilised PBPC.

Antithrombotic Therapy

The results of the first trial of intravenous abcixi-mab administered no longer than 24 h after stroke onset have recently been published.74 Abciximab is a monoclonal antibody directed against the platelet glycoprotein IIb IIIa receptor, producing blockade of the glycoprotein Ib IIIa receptor, reduction of ADP-induced platelet aggregation, and prolongation of the bleeding time.75 Doses of abciximab were similar to those used in the treatment of coronary artery disease.74 Functional outcome at 3 months was improved by abciximab. Asymptomatic parenchymal haemorrhages were more common in abciximab-treated patients, but the frequency of non-neurological bleedings was not different between the treated and placebo groups.74 Moderate thrombocytopenia occurred in 7 of abciximab patients.74 Based on preliminary encouraging results obtained with this antiplatelet agent, further trials are planned.

Antiphospholipid Syndrome And Antiphospholipid Antibodies

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent venous and arterial thrombosis, fetal loss and thrombocytopenia in association with elevated titers of circulating auto-antibodies directed against phospholipids, including lupus anticoagulant.1 Antiphospholipid antibodies (aPL) are crucial for diagnosis and represent a very heterogeneous group, as multiple specificities against various phospholipids are found. The anti-cardiolipin ELISA assay, introduced in 1983, is the most established and standardized method for detecting aPL, since other aPL directed to phosphatidylserine, phos-phatidylethanolamine, phosphatidylcholine, phos-phatidylglycerine, phosphatidylinositol and recently lysobisphosphatidic acid2 have been investigated less frequently. Moreover, in 1990 three independent groups reported the requirement of a protein cofactor, p2 glycoprotein I (p2-GPI), for efficient binding of 'autoimmune' antibodies to the phospholipids, in contrast to...

Bleeding Abnormalities

Bruising and easy bleeding have been anecdotally reported in patients on the KD (29). Berry-Kravis and colleagues (29) prospectively and retrospectively evaluated the incidence of bruising and abnormal bleeding in 51 KD patients. Sixteen (31.4 ) reported increased bruising, and 3 (5.9 ) reported bleeding problems. There was no relationship between the occurrence of these side effects and the use of other antiepileptic drugs (AEDs), and some patients with these complaints were on no other AEDs. Six of the 15 patients with increased bruising bleeding were studied in detail, including testing for platelet count, prothrombin time (PT), partial thromboplastin time (PTT), bleeding time, platelet function, and Von Willebrand disease. Five of the six had prolonged bleeding times, and all had abnormalities of platelet aggregation. One of the six patients was reevaluated off the diet, with normalization of bleeding time and platelet aggregation tests. The authors postulated that this...

Pregnancyinduced hypertension and preeclampsia

Pregnancy-induced hypertension (PIH) and pre-eclampsia are potentially severe complications of human gestation, occurring in approximately 5 of pregnancies. The clinical symptoms are hypertension, proteinurea and edema, which may be accompanied by growth retardation of the fetus. In advanced stages of the disease the patients also show cerebral symptoms, ranging from hyper-reflexia and headaches to general fits. Further, there is increased platelet activation leading to thrombopenia. Recent theories suggest that the beginning of the disease lies in a pathologically poor invasion of fetal trophoblast cells into the uterine arteries 129 . This is followed by a decreased blood supply to the placenta which then probably causes the general vasoconstriction in order to increase the placental perfusion. During the course of the disease a dysfunction of endothelial cells develops, resulting in a disorder of platelet-vessel-wall interaction which can explain many of the typical clinical...

Translating Preclinical Findings with HDAC Inhibitors to the Clinic

Nonetheless, the therapeutic benefit of HDAC inhibitors must be carefully weighed against their potential for causing toxicity. In the context of cancer, pan-HDAC inhibitors are currently regarded as effective and generally well-tolerated chemotherapeutics. Beyond nausea and fatigue, hematologic toxicity and QT prolongation have been reported with HDAC inhibitor treatment (Prince et al. 2009). Pan-HDAC inhibition can produce transient thrombocytopenia and in some instances, myelosuppression. While the class I HDAC-selective benzamides, MS-275 and MGCD0103, were notably free from significant hematologic toxicity in Phase I (Garcia-Manero et al. 2008 Gojo et al. 2007 Gore et al. 2008 Hauschild et al. 2008 Ryan et al. 2005 Siu et al. 2008), thrombocytopenia was observed with CI-994, a third class I HDAC-selective HDAC inhibitor in development (Prakash et al. 2001). Importantly, a recent study with mice in which HDAC1 and HDAC2 were conditionally deleted in bone marrow revealed that these...

Rationale For The Use Of Transdermal Systems

While the oral route (tablet, liquid) is commonly used and the preferred mode of application for patients who can take oral medication, the continuous subcutaneous (s.c.), epidural, intramuscular (i.m.) or intravenous (i.v.) mode of administration provide a faster onset, however, with a shorter duration of action. Therefore patients requiring continuous opioid analgesia and who do not experience intolerable side effects from parenteral dosing, the oral route of opioid administration is the most effective. If, however, nursing support is not possible, it may result in an inconsistent level of analgesia when the infusion rate is not controlled appropriately, or when weekly change of the infusion pump is not done in time. Contrary, the intramuscular mode of administration results in a slow absorption resulting in less variable plasma levels than the subcutaneous route, resulting in a long duration of action. However, patients who cannot take oral medication (e.g. emesis or GI...

Heparin and heparin bonded CVCs

Vascular thrombosis and subsequent systemic infection are well known to be associated with CVCs.23 Although heparin is an effective anticoagulant, it is associated with risks including autoimmune-mediated heparin-induced thrombocytopenia, allergic reactions, and the potential for bleeding it should not be used without clear evidence of benefit. A meta-analysis evaluating the effect of heparin on thrombus formation and infection in patients with CVCs and pulmonary artery catheters has been performed by Randolph et al.24 The 14 randomised controlled trials evaluated both the use of heparin and the use of heparin bonded CVCs. Heparin bonding reduces the risk of clot formation within the first 24 hours following placement of pulmonary artery catheter and is standard on most commercially available pulmonary artery catheters. For other CVCs, the combined data showed that prophylactic heparin reduced the rate of CVC related vascular thrombosis and bacterial colonisation and may decrease CVC...

Antibacterialactivity And Bacterial Resistance

Untoward effects Rifabutin generally is well tolerated in persons with HIV infection primary reasons for discontinuation of therapy include rash (4 ), GI intolerance (3 ), and neutropenia (2 ). Overall, neutropenia occurred in 25 of patients with severe HIV infection who received rifabutin. Uveitis and arthralgias have occurred in patients receiving rifabutin doses 450 mg daily in combination with clarithromycin or fluconazole. Patients should be cautioned to discontinue the drug if visual symptoms occur. Like rifampin, the drug causes an orange-tan discoloration. Rarely, thrombocytopenia, a flu-like syndrome, hemolysis, myositis, chest pain, and hepatitis have occurred.

Prdprm Complexes as Targets for Pharmacological Intervention

In light of the many processes that involve PRD PRM recognition, it was not surprising to find that ablation of these interactions by mutations are correlated with certain diseases. Liddle syndrome, a disease associated with hypertension, is caused by mutations in the PPxY motifs of the cytoplasmic domains of the amiloride epithelial sodium channel (Schild et al. 1996 Kanelis et al. 2001). The proline-rich region of huntingtin is targeted by SH3 (Qin et al. 2004) and WW domains (Holbert et al. 2001) and is likely to play a role in the progression of Huntington's disease pathogenesis. A missense mutation within the WW domain of the poly-glutamine-tract-binding protein PQBP-1 leads to Golabi-Ito-Hall syndrome, a certain type of X-linked mental retardation (Lubs et al. 2006). Mutations within the EVH1 domain of WASP affect the binding to the proline-rich ligand of the WASP-interacting protein (Volkman et al. 2002) (WIP) and are causative for Wiskott-Aldrich syndrome, an X-linked...

Interleukin2 IL2 aldesleukin proleukin

The toxicities of IL-2 likely are related to the activation and expansion of cytotoxic lymphocytes in organs and within vessels, resulting in inflammation and vascular leak, and to the secondary release by activated cells of other cytokines, such as TNF-a and interferon. When given at maximally tolerated doses of 600,000 units kg every 8 hours for up to 5 days, IL-2 causes hypotension, arrhythmias, peripheral edema, prerenal azotemia, elevated liver transaminases, anemia, thrombocytopenia, nausea, vomiting, diarrhea, confusion, and fever.

Hormones And Related Agents Glucocorticoids

In acute lymphoblastic or undifferentiated leukemia of childhood, glucocorticoids may produce prompt clinical improvement and objective hematological remissions in up to 30 of children. Although these responses frequently are characterized by complete disappearance of all detectable leukemic cells from the peripheral blood and bone marrow, the remission is brief. Remissions occur more rapidly with glucocorticoids than with antimetabolites, and there is no evidence of cross-resistance to unrelated agents. For these reasons, therapy is initiated with prednisone and vincristine, often followed by an anthracycline or methotrexate, and l-asparaginase. Glucocorti-coids are a valuable component of curative regimens for Hodgkin's disease and non-Hodgkin's lymphoma, as well as for treatment of MM and CLL. Glucocorticoids are extremely helpful in controlling autoimmune hemolytic anemia and thrombocytopenia associated with CLL.

Pharmacology and pharmaceutics

Clinical pharmacology Aldesleukin is an antineoplastic agent and biological response modifier, a highly purified human recombinant interleukin-2 (IL-2) lym-phokine. This modified IL-2 mimics the biological activities of native nonrecombi-nant IL-2. The exact mechanism by which aldesleukin mediates antitumor activity is unknown. The in vivo administration of aldesleukin in animals and humans produces multiple immunological effects in a dose-dependent manner. These effects include activation of cellular immunity with profound lymphocytosis, eosinophilia, and thrombocytopenia, and the production of cytokines, including tumor necrosis factor, IL-1 and gamma interferon. Interleukin-2 is one of several lymphocyte-produced messenger regulatory molecules that mediate immunocyte interactions and functions. The interaction of interleukin-2 with target cells occurs via a specific cell surface receptor present on T-lymphocytes and certain malignant lymphocytes.

Venous thromboembolism

Patients admitted to hospital should undergo a risk assessment for venous thromboembolism on admission. Patients considered to be at high risk include those anticipated to have a substantial reduction in mobility, those with obesity, malignant disease, history of venous thromboembolism, thrombophilic disorder, or patients over 60 years. Patients with risk factors for bleeding (e.g. acute stroke, thrombocytopenia, acquired or untreated inherited bleeding disorders) should only receive pharmacological prophylaxis when the risk of bleeding does not outweigh the risk of venous throm-boembolism. A NICE Guideline1 provides a full list of risk factors, and gives recommendations for prophylaxis. A venous thromboembolism risk assessment checklist is also available from the Department of Health (www.dh.gov.uk).

Low molecular weight heparins

Low molecular weight heparins (bemiparin, dalteparin, enoxaparin, and tinzaparin) are usually preferred over unfractionated heparin in the prevention of venous thromboembolism because they are as effective and they have a lower risk of heparin-induced thrombocytopenia see Prophylaxis of Venous Thromboembolism, p. 140. The standard prophylactic regimen does not require monitoring. The duration of action of low molecular weight heparins is longer than that of unfractionated heparin and once-daily subcutaneous administration is possible for some indications, making them convenient to use.

Thiopurines In The Treatment Of Childhood Acute Lymphoblastic Leukemia

In contrast to administration in earlier treatment elements applied in childhood ALL protocols (e.g., consolidation or extra-compartment therapy) where thiopurines are given at fixed doses, in maintenance both 6-MP and methotrexate doses are adjusted according to absolute leukocyte or neutrophil and platelet counts. Current BFM dose modification guidelines for maintenance treatment in childhood ALL call for an absolute leukocyte count in a target range of 2-3 x 109 L (2, 57). Minimal requirements for starting maintenance treatment are an absolute leukocyte count of 1 x 109 L with at least 0.2 x 109 L neutrophils and 50 x 109 L thrombocytes (counts not decreasing). With regard to the debate about the better thiopurine, there are three published randomized studies comparing the toxicity and efficacy of 6-TG with 6-MP in interim maintenance and maintenance therapy of childhood ALL. The first published trial randomized 474 patients with childhood ALL to either 6-TG or 6-MP in maintenance...

Clinical Use Of Vasopressin Peptides

V2 receptor agonists (e.g., desmopressin) are also used in bleeding disorders. In most patients with type I von Willebrand's disease (vWD) and in some with type Iln vWD, desmopressin will elevate von Willebrand factor and shorten bleeding time. However, desmopressin generally is ineffective in patients with types IIa, IIb, and III vWD. Desmopressin may transiently cause a marked thrombocytopenia in individuals with type IIb vWD and is contraindicated in such patients. Desmo-pressin also increases factor VIII levels in patients with mild-to-moderate hemophilia A. Desmopressin is not indicated in patients with severe hemophilia A, those with hemophilia B, or those with factor VIII antibodies. The response of any given patient with type I vWD or hemophilia A to desmopressin should be determined with a test dose of nasal spray at the time of diagnosis or 1-2 weeks before elective surgery to assess the extent of increase in factor VIII or von Willebrand factor. In patients with renal...

The Interleukins Aldesleukin129

Aldesleukin enhances lymphocyte mitogenesis and stimulates long-term growth of human IL-2-dependent cell lines. IL-2 also enhances the cytotoxicity of lymphocytes. Induction of NK cell and lymphocyte-activated killer (LAK) cell activity occurs, as does induction of production. In mouse and human tumor cell lines, aldesleukin activates cellular immunity in patients with profound lymphocytosis, eosinophilia, and thrombocytopenia. Aldesleukin also activates the production of cytokines, including tumor necrosis factor (TNF), IL-1, and IFN-y. In vivo experiments in mouse tumor models have shown inhibition of tumor growth. The mechanism of the antitumor effect of aldesleukin is unknown.

Miscellaneous Agents Hydroxyurea

The principal use of HU has been as a myelosuppressive agent in myeloproliferative syndromes, particularly in essential thrombocythemia with platelet counts 1.5 million cells mm3 or history of arterial or venous thrombosis. It dramatically lowers the risk of thrombosis by lowering the platelet count, through its effect on neutrophil and red cell counts, and by reducing L-selectin expression and increasing NO production of neutrophils. Hematopoietic depression involving leukopenia, megaloblastic anemia, and occasionally thrombocytopenia is the major toxic effect bone marrow recovery usually is prompt if the drug is discontinued for a few days. Other adverse reactions include a desquamative interstitial pneumonitis, GI disturbances, and mild dermatological reactions. More rarely, stomatitis, alopecia, and neurological manifestations have occurred. Increased skin and fingernail pigmentation and painful leg ulcers may occur. Hydroxyurea has uncertain effect on the risk of secondary...

Dietary Longchain Polyunsaturated Fatty Acids In A Ketogenic Diet Clinical Challenges

The optimal dosage and composition of the LC-PUFA supplement must be determined. Preliminary evidence suggests that only nonesterified forms of these fatty acids are effective (31), and this needs to be considered. Only one clinical study has assessed the antiseizure effects of a PUFA supplement in epilepsy patients (29). In this study, patients were given 3.25 g of an o 3 PUFA supplement (2.3 g of DHA, 0.9 g of EPA, and 0.05 g of ALA) daily. Although this dosage resulted in a reduction in seizure frequency and was not associated with any adverse effects, the epilepsy patients studied were not being treated with a KD. Because bruising is one of the common side effects of the KD, being experienced by 31 of KD patients (46), it is possible that o 3 PUFA supplementation may exacerbate this condition. Thus, the acute and long-term effects of various doses of o 3 LC-PUFA on factors such as platelet count, platelet aggregation, and bleeding time in KD subjects must be defined. Berry-Kravis...

Oprelvekin Recombinant131132

Oprelvekin is indicated for the prevention of severe thrombocytopenia. It reduces the need for platelet transfusions after myelosuppressive chemotherapy in patients with nonmyeloid malignancies who are at high risk for severe thrombocytopenia. Efficacy has been demonstrated in persons who have experienced severe thrombocytopenia following a previous chemotherapy cycle.

Clinical Pharmacology Nitrogen Mustards

The major acute toxic manifestations of mechlorethamine are nausea and vomiting, lacrimation, and myelosuppression. Leukopenia and thrombocytopenia limit the amount of drug that can be given in a single course. Like other alkylating agents, mechlorethamine blocks reproductive function and may produce premature ovarian failure in women and oligospermia in men. Since fetal abnormalities can be induced, this drug should not be used in the first trimester of pregnancy and should only be used with caution in later stages of pregnancy. Breast-feeding must be stopped before therapy with mechlorethamine is initiated.

Toxic Side Effects of As2O3

Instead, As2O3 induces leukocytosis in about 50 of patients.11,13,36 The leuko-cytosis can resolve in all cases without chemotherapy.87 The APL patients on As2O3 can also develop retinoic acid syndrome (RAS)-like symptoms such as fever, skin rash and edema, which can be readily relieved by steroid administra-tion.88 Other mild effects were reported in about 40-50 of relapsed patients, including fatigue, fever, edema, nausea, anorexia, diarrhea, emesis, headache, insomnia, cough, dyspnea, dermatitis, tachycardia, pain, hypokalemia, hypo-magnesemia and hyperglycemia. The most common ( 10 ) Grade 3 and 4 adverse events were abdominal pain, epistaxis, dyspnea, hypoxia, bone pain, thrombocytopenia, neutropenia, hypokalemia and hyperglycemia.11,36,89 In a clinical trial, prolonged QT intervals (the time intervals for the contraction of the ventricle from the beginning of the Q wave to the end of T wave a prolonged QT interval indicates cardiac toxicity) were observed in all patients during...

Antitumor Activity of Carboplatin Oxaliplatin and Nedaplatin

Nedaplatin is registered for use in head and neck, testicular, lung, esopha-geal, ovarian and cervical cancers in Japan. A randomized clinical trial has revealed that nedaplatin is cross-resistant with cisplatin, but less toxic.9 It has shown no marked advantage over cisplatin in objective response and overall survival. More thrombocytopenia, but less leucopenia, nephrotoxicity and gastrointestinal toxicity were observed.

Consequences Of Antibodies To Therapeutic Proteins

In the case of interferon beta treatment of multiple sclerosis the loss of efficacy is much more difficult to measure because the mode of action of the therapeutic protein is not known and the disease progress is unpredictable and difficult to monitor. The reduction of Mx induction which is specific for interferon activity has been used successfully to evaluate the biological effect of antibodies to interferon beta. The adverse effects of therapeutic proteins are in general the result of an exaggerated pharmacodynamic effect. So the loss of side effects may also be the result of the induction of antibodies and may be the first sign of immunogenicity. For example, in patients treated with interferon the loss of flulike symptoms is associated with the appearance of antibodies. Because by definition neutralizing antibodies interact with ligand-receptor interaction, they will inhibit the efficacy of all products in the same class with serious consequences for patients if there is no...

Fourthgeneration Cephalosporins

(no longer available in U.S.) have produced acute tubular necrosis, and usual doses (8-12 g day) have caused nephrotoxicity in patients with preexisting renal disease. Diarrhea can result from the administration of cephalosporins and may be more frequent with cefoperazone, perhaps because of its greater biliary excretion. Intolerance to alcohol has been noted. Serious bleeding related either to hypoprothrombinemia, thrombocytopenia, and or platelet dysfunction has been reported.

Neurolytic Visceral Sympathetic Blocks

Before performing any neurolytic block the physician should obtain pain history, and physical examination with identification of cancer as the main reason of pain. Neurological examination is mandatory before performing neurolytic blocks in order to identify any preexisting neurological deficit. The physician should perform examination of the site of the block to identify the presence of any infection and obtain coagulation profile including PT, INR, PTT, and platelet count because some of the cancer medications can affect platelets function and coagulation factors. The patient should have received appropriate trials of opioid and there should be a documentation of intolerance to opioids or ineffectiveness of opioids in relieving pain, despite increasing the dose. The physician should also obtain informed consent, explain in detail the procedure to the patient and also to the family if required, explain in detail and document all the risks and benefits of the blocks including the...

HDACi and Foxp3 Tregs

The clinical use of many pan-HDACi is associated with a common adverse effect profile of cardiac QT prolongation, nausea, diarrhea, vomiting, hypokalemia, loss of appetite and thrombocytopenia, plus in many cases, profound and debilitating fatigue. Likewise, their ability to induce cytotoxicity is considered a key and highly desirable action in the context of malignancies, which often overexpress HDAC1 and HDAC2, but the toxicity profile and cytotoxic effects render these agents far less suitable for nononcologic applications. To that end, various groups are seeking to avoid the class-associated side effects of pan-HDACi by trying to design isoform-selective HDACi for use in oncology and inflammation.

Methylenetetrahydrofolate Reductase Mthfr

While these studies did not show an association between MTHFR polymorphisms and toxicity, prior adult studies have shown a possible association between MTHFR polymorphisms and chemotherapy toxicity (9) or with MTX graft versus host disease prophylaxis in adult bone marrow transplant (10). Costea et al. recently reported that children with the MTHFR 677 CC genotype had significantly less grade 3 leukopenia when treated on DFCI ALL protocols (11). Likewise, patients with the CCND1 870 AA genotypes had significantly less grade 3 leukopenia, grade 2 thrombocytopenia, and grades 3 and 4 transaminase elevation.

Thrombopoietic Growth Factors

The drug is administered at 25-50 mg kg day subcutaneously. Oprelvekin is approved for use in patients undergoing chemotherapy for nonmyeloid malignancies who display severe thrombocytopenia (platelet count 100,000 ,mL. The major complications of therapy are fluid retention and associated cardiac symptoms, such as tachycardia, palpitation, edema, and shortness of breath this is a significant concern in elderly patients and often requires concomitant therapy with diuretics. Fluid retention reverses upon drug discontinuation, but volume status should be carefully monitored in elderly patients, those with a history of heart failure, or those with preexisting pleural or pericardial effusions or ascites. Also reported are blurred vision, injection-site rash or erythema, and paresthesias. Results with these agents have been mixed. In cancer patients, recombinant human throm-bopoietin therapy has reduced the duration of severe thrombocytopenia and the need for platelet transfusions. On the...

Gestational hypertension preeclampsia and eclampsia

Gestational hypertension is the most frequent cause of hypertension during pregnancy and the rate varies between 6 and 17 .14,15 Some women with gestational hypertension will subsequently progress to preeclampsia and the rate of progression depends on gestational age at the time of diagnosis. The rate reaches 50 when gestational hypertension develops before 30 weeks gestation. Preeclampsia is primarily defined as gestational hypertension plus proteinuria. Preeclampsia is considered severe if there is severe gestational hypertension in association with proteinuria (in the normal kidney, during the filtration process that takes place in the glomerulus, proteins do not enter the urinary space and the presence of proteins in urine is always a sign of glomerular disease) or in the presence of multiorgan involvement such as pulmonary edema (i.e. the passage of fluids from the pulmonar interstitial compartment to the alveolar lumen causing a severe obstacle to the diffusion of oxygen from...

Fludarabine Phosphate

Toxic manifestations include myelosuppression, nausea and vomiting, chills and fever, malaise, anorexia, and weakness. Lymphopenia and thrombocytopenia are dose limiting and possibly cumulative. CD4+ T cells are depleted with therapy. Opportunistic infections and tumor lysis syndrome have been reported. Peripheral neuropathy may occur at standard doses. Altered mental status, seizures, optic neuritis, and coma have been observed at higher doses and in older patients. Rarely, CLL patients may develop an acute hemolytic anemia or pure red cell aplasia during fludarabine treatment. Severe pneumonitis responsive to glucocorticoids has been encountered. Because a significant fraction of drug ( 25 ) is eliminated in the urine, patients with compromised renal function should be treated with caution, and initial doses should be reduced proportionate to serum creatinine levels.

Liquid Liquid Extraction

Sirolimus is a potent immunosuppressive agent. To prevent thrombocytopenia and hypercholesterolemia, optimize efficacy, and reduce organ rejection, assays were developed to monitor concentrations of sirolimus in the whole blood of patients under treatment.40-42 Wallemacq et al.43 developed and validated a simple high-throughput HPLC-MS MS method to routinely monitor sirolimus

Thrombopoietin

Despite being named in 1958 (90), TPO was not isolated until 1994 when this was achieved simultaneously by five groups (91-95). TPO is the seminal regulator of platelet production, which, like M-CSF and G-CSF, is consumed by its target cells (megakaryocytes and platelets) that express the c-mpl receptor (57,58). Two forms of recombinant human TPO were initially examined in clinical studies a full-length and glycosylated molecule that is equivalent to the native growth factor (rHuTPO) and a truncated and pegylated version known as megakaryocyte growth and development factor (MGDF). None of these firstgeneration agents attained regulatory approval mainly because of the production of antibodies by the human immune system that were directed against the administered therapeutic (96,97). These antibodies were also capable of neutralizing endogenous TPO causing extended-term refractory thrombocytopenia. This spurred the creation of novel mpl ligands, seven of which have been recently...

DAB388QMCSF or DTQM

Pre-clinical studies have also been conducted in cynomolgus monkeys in order to determine the toxicity and pharmacokinetics of DTGM within a primate model. In contrast to the mouse, the cynomolgus monkeys possess cross-reactive GM-CSF receptors. As reported by Hotchkiss et al. (1999), four groups of young adult monkeys were treated over a five consecutive day dosing regimen with doses ranging from 1, 5, 7.5 to 10 g kg day. Monkeys treated with 1 g kg day showed no side effects. At doses of 5 g kg day, mild thrombopenia was present. At doses of 7.5 g kg day, neutropenia, thrombopenia, anemia, and hypoalbu-minemia was present. At the maximal dose of 10 g kg day, severe neutropenia, thrombopenia, anemia, and hypoalbuminemia was present. Three out of the four monkeys in this group died from sepsis. Autopsies on all four monkeys in this group revealed marked apoptosis and hypoplasia in the bone marrow. No injury to other organs, including the kidney, heart, liver, lungs, and central...

Chromium

Chromium is generally well tolerated however, some patients may experience nervous system symptoms such as perceptual, cognitive, and motor dysfunction with doses as low as 200-400 ig (Fox and Sabovic 1998). In addition, toxicity has been reported with chromium consumption. In one case a woman developed anemia, thrombocytopenia, hemolysis, weight loss, and liver and renal toxicity when attempting to lose weight with 1,200-2,400 ig of chromium picolinate. These problems resolved after discontinuation of chromium ingestion (Cerulli et al. 1998). A lower dose of only 600 ig was demonstrated to have resulted in interstitial nephritis in another female patient (Wasser et al. 1997).

Autoimmunity

The safety and clinical and biological effects of CD5 + in patients with systemic lupus erythematosus (SLE) was studied by Stafford et al. (1994) in a Phase I study. A dose of 0.1 mg kg was administered intravenously on five consecutive days. A second course of immunoconjugate was given to patients who failed to show any clinical response 1-2 months later. Six patients (4 with glomerulonephritis and 2 with thrombocytopenia) were studied. Improvement was documented in 2 patients with nephritis no effect on thrombocytopenia was observed. Adverse effects were mild and transient. Relative to pretreatment lymphocyte counts, the mean reduction in CD3+ T-cell count was 69 at 2 weeks, 32 at 1 month and 34 at 6 months following initial treatment. There was a transient decrease in CD5 + B cells, but no persistent depletion of total B-cell numbers. Thus, anti-CD5 RTA immunoconjugate is well tolerated in patients with SLE, causes modest T-cell depletion which may persist for months, and may have...

Blood disorders

Side-effects Side-effects of the aminosalicylates include diarrhoea, nausea, vomiting, abdominal pain, exacerbation of symptoms of colitis, headache, hyper-sensitivity reactions (including rash and urticaria) side-effects that occur rarely include acute pancreatitis, hepatitis, myocarditis, pericarditis, lung disorders (including eosinophilia and fibrosing alveolitis), peripheral neuropathy, blood disorders (including agranulo-cytosis, aplastic anaemia, leucopenia, methaemoglobin-aemia, neutropenia, and thrombocytopenia see also recommendation above), renal dysfunction (interstitial nephritis, nephrotic syndrome), myalgia, arthralgia, skin reactions (including lupus erythematosus-like syndrome, Stevens-Johnson syndrome), alopecia.

Enoximone

Output reduced and filling pressures increased Cautions heart failure associated with hypertrophic cardiomyopathy, stenotic or obstructive valvular disease or other outlet obstruction monitor blood pressure, heart rate, ECG, central venous pressure, fluid and electrolyte status, renal function, platelet count, hepatic enzymes avoid extravasation interactions Appendix 1 (phosphodiesterase type-3 inhibitors) Hepatic impairment dose reduction may be required Renal impairment consider dose reduction Pregnancy manufacturer advises use only if potential

Lepirudin

Indications Anticoagulation in patients with heparin-induced thrombocytopenia and associated thromboembolic disease in order to prevent further thromboembolic complications B. Indications and use Refludan is indicated for anticoagulation in patients with heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease in order to prevent further thromboembolic complications.

M Terazosin

Driving May affect performance of skilled tasks e.g. driving Pregnancy no evidence of teratogenicity manufacturers advise use only when potential benefit outweighs risk Breast-feeding no information available Side-effects see section 7.4.1 also reported weight gain, dsypnoea, paraesthesia, nervousness, decreased libido, thrombocytopenia, back pain, and pain in extremities Dose

Untoward Effects

With confusion and hallucinations, nephrotoxicity, and uncommonly, severe thrombocytopenia, sometimes fatal, in immunocompromised patients. Acyclovir has been associated with neutropenia in neonates. Chronic acyclovir suppression of genital herpes has been used safely for up to 10 years. No excess frequency of congenital abnormalities is recognized in infants born to women exposed to acyclovir during pregnancy.

Investigations

The laboratory features in RA reflect the acute-phase response and chronic inflammation of the joints and are listed in Box 38.2. Anemia, thrombocytopenia, leukope-nia, or abnormal liver function tests may also be caused by drug toxicity.The earliest radiographic changes are seen in the hands in the form of soft-tissue swelling and periarticular osteopenia, but these are nonspecific signs. Erosions typical of RA develop in bare areas of bone

Therapeutic Uses

In HIV-infected persons, IFNs have antiretroviral effects, but, the combination of zidovudine and IFN gave only transient benefit and excessive hematological toxicity. IFN-a (3 million units three times weekly) is effective for HIV-related thrombocytopenia resistant to zidovudine therapy.

Eligibility Criteria

Pts with a cytologically or histologically confirmed advanced or recurrent gastric cancer refractory to conventional therapy were candidates for this study. Pts with a serious infection including HBsAg, HCVab, syphilis, HIV positive, uncontrollable hypertension, brain metastasis showing symptoms, allergy against anthracycline-type drugs, cardiofunction disorders (e.g., pt with suspected congestive heart failure, pt with a treatment history of congestive heart failure, pt with a history of myocardial infarction, and pt with an electrocardiographic abnormality who requires pharmacotherapy.), vascular disorder including a history of pulmonary embolism, deep venous thrombosis, and peripheral artery occlusive disease were excluded. Pts were also excluded if they were pregnant or lactating, or showing gastrointestinal bleeding. Also, pts for whose principal investigator or investigators considered ineligible were excluded. Eligibility criteria also included the following (1) World Health...

Heparin

Pregnancy Heparins are used for the management of venous thromboembolism in pregnancy because they do not cross the placenta. Low molecular weight hepar-ins are preferred because they have a lower risk of osteoporosis and of heparin-induced thrombocytopenia. Low molecular weight heparins are eliminated more rapidly in pregnancy, requiring alteration of the dosage regimen for drugs such as dalteparin, enoxaparin, and tinzaparin see also under individual drugs. Treatment should be stopped at the onset of labour and advice sought from a specialist on continuing therapy after birth.

M Danaparoid Sodium

Indications prevention of deep-vein thrombosis in general or orthopaedic surgery thromboembolic disease in patients with history of heparin-induced thrombocytopenia Cautions recent bleeding or risk of bleeding concomitant use of drugs that increase risk of bleeding antibodies to heparins (risk of antibody-induced thrombocytopenia) body-weight over 90 kg (monitor anti factor Xa activity) Contra-indications haemophilia and other haemor-rhagic disorders, thrombocytopenia (unless patient has heparin-induced thrombocytopenia), recent cerebral haemorrhage, severe hypertension, active peptic ulcer (unless this is the reason for operation), diabetic retinopathy, acute bacterial endocarditis, spinal or epidural anaesthesia with treatment doses of danaparoid Renal impairment caution in moderate impairment increased risk of bleeding (monitor anti-Factor Xa activity) avoid in severe impairment unless patient has heparin-induced thrombocytopenia and no alternative available Pregnancy manufacturer...

Hirudins

Lepirudin, a recombinant hirudin, is licensed for anticoagulation in patients with Type II (immune) heparin-induced thrombocytopenia who require parenteral anti-thrombotic treatment. The dose of lepirudin is adjusted according to activated partial thromboplastin time (APTT). Bivalirudin, a hirudin analogue, is a thrombin inhibitor which is licensed for acute coronary syndromes in patients planned for urgent or early intervention, and as an anticoagulant for patients undergoing percutaneous coronary intervention (see also section 2.10.1) bivalirudin should be administered in combination with aspirin and clopidogrel. The Scottish Medicines Consortium (p. 4) has advised (November 2008) that bivalirudin (Angiox ) is accepted for restricted use within NHS Scotland for patients with acute coronary syndromes planned for urgent or early intervention who would have been considered for treatment with unfractionated heparin in combination with a glycopro-tein IIb IIIa inhibitor it should not be...

M Lepirudin

Indications thromboembolic disease requiring par-enteral anticoagulation in patients with heparin-induced thrombocytopenia type II Cautions recent bleeding or risk of bleeding including recent puncture of large vessels, organ biopsy, recent major surgery, stroke, bleeding disorders, severe hypertension, bacterial endocarditis concomitant use of drugs that increase risk of bleeding determine activated partial thromboplastin time 4 hours after start of treatment (or after infusion rate altered) and at least once daily thereafter Hepatic impairment no information manufacturer

M Abciximab

Indications prevention of ischaemic cardiac complications in patients undergoing percutaneous coronary intervention short-term prevention of myocardial infarction in patients with unstable angina not responding to conventional treatment and who are scheduled for percutaneous coronary intervention (use under specialist supervision) Cautions measure baseline prothrombin time, activated clotting time, activated partial thromboplastin time, platelet count, haemoglobin and haematocrit monitor haemoglobin and haematocrit 12 hours and 24 hours after start of treatment and platelet count 24 hours and 24 hours after start of treatment concomitant use of drugs that increase risk of bleeding discontinue if uncontrollable serious bleeding occurs or emergency cardiac surgery needed consult product literature for details of procedures to minimise bleeding elderly Contra- nd cat ons active internal bleeding major surgery, intracranial or intraspinal surgery or trauma within last 2 months stroke...

Thalidomide

Interleukin-2 Human recombinant IL-2 (aldesleukin, proleukin des-alanyl-1, serine-125 human IL-2) differs from native IL-2 in that it is not glycosylated, has no amino terminal Ala, and has an Ser substituted for the Cys at amino acid 125. The potency of the preparation is represented in International Units in a lymphocyte proliferation assay such that 1.1 mg of recombinant IL-2 protein equals 18 million International Units. Aldesleukin has the following in vitro biologic activities of native IL-2 enhancement of lymphocyte proliferation and growth of IL-2-dependent cell lines enhancement of lymphocyte-mediated cytotoxicity and killer cell activity and induction of interferon- activity. In vivo administration of aldesleukin in animals produces multiple immunologic effects in a dose-dependent manner. Cellular immunity is profoundly activated with lymphocyto-sis, eosinophilia, thrombocytopenia, and release of multiple cytokines (e.g., TNF-a, IL-1, interferon- ). Aldesleukin is indicated...

Cerezyme

Type 1 Gaucher disease is a hereditary condition occurring in about 1 40,000 individuals. It is characterized by a functional deficiency in j-glucocerebrosidase enzyme activity and the resulting accumulation of lipid glucocerebroside in tissue macrophages, which become engorged and are termed Gaucher cells. Gaucher cells typically accumulate in the liver, spleen, and bone marrow and, occasionally, in lung, kidney, and intestine. Secondary hematological sequelae include severe anemia and thrombocytopenia in addition to characteristic progressive hepatosplenomegaly. Skeletal complications are common and are frequently the most debilitating and disabling feature of Gaucher disease. Possible skeletal complications are osteonecrosis, osteopenia with secondary pathological fractures, remodeling failure, os-teosclerosis, and bone crises.

Oprelvekin

Indications Prevention of severe thrombo-cytopenia and the reduction of the need for platelet transfusions following myelosup-pressive chemotherapy in patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia B. Indications and use Neumega is indicated for the prevention of severe throm-bocytopenia and the reduction of the need for platelet transfusions following myelo-suppressive chemotherapy in patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia. It reduces the need for frequent platelet transfusions following high-dose chemotherapy. While platelet transfusions are safe, they carry small risks of infectious disease transmission as well as a small risk of bacterial contamination during storage. Also, transfusions often need to be repeated frequently in an in-patient setting, and may delay chemotherapy.

Vincristine

The clinical toxicity of vincristine is mostly neurological. The more severe neurological manifestations may be avoided or reversed either by suspending therapy or reducing the dosage upon occurrence of motor dysfunction. Severe constipation may be prevented by a prophylactic program of laxatives and hydrophilic (bulk-forming) agents and usually is a problem only with doses above 2 mg m2. Alopecia occurs in 20 of patients given vincristine however, it is always reversible, frequently without cessation of therapy. Although less common than with vinblastine, leukopenia may occur with vincristine, and thrombocytopenia, anemia, polyuria, dysuria, fever, and GI symptoms have been reported occasionally. The syndrome of inappropriate secretion of antidiuretic hormone occasionally has occurred during vincristine therapy. In view of the rapid action of the vinca alkaloids, it is advisable to prevent hyperuricemia by the administration of allopurinol. Vinorelbine (navelbine, others) is...

Doxorubicin

The toxic manifestations of doxorubicin are similar to those of daunorubicin. Myelosuppres-sion is a major dose-limiting complication, with leukopenia usually reaching a nadir during the second week of therapy and recovering by the fourth week thrombocytopenia and anemia follow a similar pattern but usually are less pronounced. Stomatitis, GI disturbances, and alopecia are common but reversible. Erythematous streaking near the site of infusion ( adriamycin flare ) is a benign local allergic reaction and should not be confused with extravasation. Facial flushing, conjunctivitis, and lacrimation may occur rarely. The drug may produce severe local toxicity in irradiated tissues (e.g., the skin, heart, lung, esophagus, and GI mucosa). Such reactions may occur even when the two therapies are not administered concomitantly.

Triazenes

Phase of disappearance (t1 2 20 minutes), dacarbazine is removed from plasma with a terminal t1 2 of 5 hours. The t1 2 is prolonged in the presence of hepatic or renal disease. Almost 50 of the compound is excreted intact in the urine by tubular secretion. Elevated urinary concentrations of 5-aminoimidazole-4-carboxamide are derived from the catabolism of dacarbazine, rather than by inhibition of de novo purine biosynthesis. Dacarbazine (dtic-dome, others) for malignant melanoma is given in doses of 3.5 mg kg day, intravenously, for a 10-day period, repeated every 28 days. Alternatively, 250 mg m2 can be given daily for 5 days and repeated every 3 weeks. Extravasation of the drug may cause tissue damage and severe pain. At present, dacarbazine is employed in combination regimens for the treatment of Hodgkin's disease. It is less effective against malignant melanoma and adult sarcomas. The toxicity of DTIC includes nausea and vomiting in 90 of patients vomiting usually develops 1-3...

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