A slide about this is a BLEEDING DISORDERS.pptx

A slide about this is a BLEEDING DISORDERS.pptx

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  PLATELETS DISORDERS DR BETTYA KASIMO
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  Introduction • For effectivehemostasis, an adequate number of functional platelets are required. • Any decrease in platelet number (thrombocytopenia) or impairment of platelet function results in excessive bleeding following injury. • Bleeding time relies on adequate platelet numbers and function rather than fibrin formation. • So, it is a good guide to test the efficiency of primary hemostasis and is not usually affected by deficiencies of clotting factors.
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  Classification of plateletDisorders • They can be classified as quantitative( number of platelets) and qualitative(platelet function) • Quantitative platelet disorders • Thrombocytopenia due to; • Increased destruction • Decreased production • Sequestration • Dilutional • Thrombocytosis
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  Classification of plateletDisorders • Qualitative platelet disorders • Hereditary; due to • Defective adhesion of platelets • Disorders of platelet secretion • Defective platelet aggregation • Acquired
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  Thrombocytopenia • Decrease inthe platelet count below the lower limit of 150,000/cu mm (150 × 109/L) • Causes: Increased destruction, decreased production, sequestration and dilutional • Increased platelet destruction; it can be immune and Non-immune mediated • Immune mediated • Autoimmune– Primary: Immune thrombocytopenic purpura (acute and chronic)– Secondary: Systemic lupus erythematosus, B cell lymphoid neoplasms • Alloimmune: Post-transfusion or pregnancy • Drug-induced: Quinidine, heparin, sulfa compounds • Infections: HIV infection, infectious mononucleosis, cytomegalovirus •
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  Contn • Non-immune mediated •DIC; platelets are activated and consumed due to activation of the coagulation system within the blood vessels • Thrombotic thrombocytopenic purpura, hemolytic uremic syndrome; platelets are activated and consumed without activation of coagulation system. • Mechanical destruction: pts with prosthetic heart valve and diffuse narrowing of the microvasculature as in malignant
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  Causes of thrombocytopenia •Decreased production of platelets; • Generalized primary diseases of bone marrow: Aplastic anemia , fanconi anemia (congenital and acquired) • Bone marrow invasion/infiltration: Leukemia, disseminated cancer • Selective impairment of platelet production • Drug-induced: Alcohol, thiazides, cytotoxic drugs • Infections: Measles, human immunodeficiency virus (HIV) • Ineffective megakaryopoiesis; Because of impaired DNA synthesis in nutritional deficiency of vitamin B12 or folic acid.
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  Causes of thrombocytopenia •Sequestration/excessive pooling of platelets • Normally, 65 to 70% of platelets are circulating and 30 to 35% are sequestered in spleen. • Hypersplenism: It is a syndrome which is associated with increased sequestration/pooling of platelets (up to 80%) in the spleen causing thrombocytopenia • Dilutional; Massive blood transfusions can produce dilutional thrombocytopenia and also occurs frequently during the third trimester of pregnancy
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  Clinical presentation • Bleeding,gum bleeding, nose bleeding • Easy bruising • Prolonged bleeding from cut injuries • Petichiae; Small red or purple spots on the skin due to minor hemorrages
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  Investigations • CBC • Peripheralblood smear; look at morphology for any abnormalities • Bone marrow aspiration and biopsy • Coagulation studies • LFTs • Viral serology • Platelet antibody testing • Flow cytometry
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  Treatment • Identify theunderly cause and treat accordingly • Platelet transfusion • Medication like corticosteroids and immunoglobulins increase platelet count • Among others
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  Idiopathic (Immune) Thrombocytopenic Purpura(ITP) • ITP is the most common form of thrombocytopenia as well as common form of immune thrombocytopenia. • There is increased destruction of platelets by mainly by autoimmune mechanism, hence also referred to as autoimmune thrombocytopenia • Acute immune thrombocytopenic purpura • Acute ITP is a self-limited disease of children between 2 to 4 years and occurs with equal • frequency in both sexes. • It often presents 1 to 3 weeks after viral (measles, rubella, EBV) infection. • Platelet destruction is caused by antiplatelet autoantibodies, drugs eg Heparin, viruses like HIV • These are IgM type of antibodies that combine with platelets and result in destruction of platelets in the spleen. • Platelet count is decreased, sometimes even below 10,000/cu mm (10 × 109/L)
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  Chronic immune thrombocytopenicpurpura • Chronic ITP is defined as persistent thrombocytopenia lasting more than 6 to 12 months. • This is an indolent and more common form of primary ITP usually seen in adults. • Chronic ITP is more common in females (F:M ratio is 3:1) between 20 and 40 yrs. Pathogenesis • Chronic ITP is an autoimmune disorder with formation of antiplatelet antibodies, directed • against membrane glycoproteins most often IIb-IIIa or Ib-IX of platelets. • The antiplatelet antibodies can be demonstrated in approximately 80% of patients and are of the IgG type. • The mechanism of platelet destruction is similar to that seen in autoimmune hemolytic anemias.
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  Contn • The antiplateletantibodies act as opsonins and are recognized by IgG Fc receptors • present on mononuclear phagocytes of RE system (mainly spleen) and are destroyed there resulting in thrombocytopenia • Spleen is not only the major site of destruction of platelets but also important site of autoantibody synthesis. • Thus, splenectomy shows marked improvement in about 75 to 80% of patients
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  Lab investigation • Plateletcount: Markedly reduced and is below 80,000/cu mm (80 × 109/L). • Hemoglobin: The level varies depending on the duration and amount of bleeding and rangesfrom 7 to 12 gm/dL. Peripheral smear: • Platelets: There is marked reduction in their number (thrombocytopenia). Accelerated compensatory thrombopoiesis often leads to the formation of abnormally large sized platelets (megathrombocytes/giant platelets)
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  Lab investigation • RBCs:Anemia develops in patients who have appreciable blood loss over a period of months to years. • Chronic loss of blood may result in microcytic hypochromic anemia, especially in females with menorrhagia. • WBCs: Usually within normal range. • Bone marrow; Cellularity: Bone marrow is hypercellular. • Megakaryopoiesis: Bone marrow shows moderate increase in number of both immature and mature forms of megakaryocytes.
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  Contn • Erythropoiesis: Bleedingfrom thrombocytopenia may result in anemia accompanied by normoblastic erythroid hyperplasia. • With constant bleeding, iron deficiency may result in micronormoblastic erythroid hyperplasia. • Myelopoiesis: Normal • Storage iron: In patients with severe and chronic bleeding iron deficiency develops resulting in depletion of iron stores. • Bleeding time (BT): Prolonged, but PT and PTT are normal. • Tourniquet test: Positive • Clotting time (CT): Normal • Tests for platelet autoantibodies: May be positive
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  Thrombotic thrombocytopenic purpura •It’s a rare disorder characterized by the formation of clots in the small blood vessel throughout the body • Key findings; • 1 thrombocytopenia, • 2 microangiopathic hemolytic anemia; fragmentation of RBCs due to passing through small vessels with clots • 3 renal failure; kidney damage due to clot formation • 4 neurological symptoms; confusion, seizures • 5 fever
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  Causes • ADAMTS13 deficiency;This enzymes breaks down the von wilbrand factor which mediates platelet adhesions • Autoimmune disorder; autoantibodies against ADAMTS13 can cause TTP • Infections can trigger TTP Mgt Plasma exchange is the primary treatment for TTP; aims at removing autoantibodies Immunosuppressive therapy
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  HUS (Hemolytic uremicsyndrome) • It’s a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. • Causes ; • shiga toxin-producing E. coli; common cause HUS in children • Infections with Srep Pneumonaie can also trigger HUS • Genetic mutations in the compliment regulatory proteins
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  Pathogenesis of HUS •Patients with HUS have normal levels of vWF metalloprotease, indicating a different pathogenesis than that of TTP. • HUS develops following damage to the endothelium by toxins, drugs or radiation. • One main cause of HUS in children and the elderly is infectious gastroenteritis caused by Escherichia coli strain 0157:H7. • E. coli produces a Shiga-like toxin which is absorbed from the inflamed gastrointestinal mucosa. • The toxin enters circulation and damages endothelial cells of microvasculature, mainly in the renal glomerular capillaries and initiates platelet activation and thrombi formation.
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  Contn • Red cellsget trapped in the formed thrombi, undergo fragmentation resulting in schistocytes. • Splenic trapping of the fragmented red cells causes extravascular hemolysis. • Clinically, HUS develops in children few days after a bloody diarrhea. • Oliguria, anuria and electrolyte imbalance, hemolytic anemias and low platelets • With appropriate supportive care, they usually recover completely but in more severe cases renal damage may result in death. • HUS can also develop in adults following certain drugs and radiation therapy that damage endothelial cells.
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  Laboratory diagnosis ofthrombotic microangiopathies • Hemoglobin: Decreased usually less than 6 gm/dL. • Platelet count: Markedly reduced often below 20,000/cu mm (20 × 109/L). • Peripheral smear • RBCs: Show fragmented red cells (schistocytes), nucleated RBCs and microspherocytes. • WBCs: Show mild leukocytosis with a shift to left. • Platelets: Markedly reduced. • Reticulocyte count: Increased. • Prothrombin time (PT) and activated partial thromboplastin time (APTT) are usually normal • Urine: Shows moderate proteinuria and both gross and microscopic hematuria
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  Thrombocytosis • Elevated plateletcount • There are two types; primary and secondary • Primary thrombocytosis; caused by neoplasm e.g Essential thrombocythemia • Secondary is often caused by underlying conditions like infection, inflammation or iron deficiency . • Asymtomatic, though increased risk of thrombosis and bleeding rarely occurs • Treat the underly cause and cytoreductive therapy (Hydroxyurea and interferon – alpha) may reduce platelet count and thrombotic risk.
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  Qualitative disorders • Qualitativedisorders of platelet function produce defects in the formation of hemostatic plug and thus result in bleeding. • These disorders are characterized by prolonged bleeding time and normal platelet count. • Qualitative defects of platelet function can be hereditary/congenital or acquired
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  Classification of thequalitative Disorders of platelets • Hereditary • 1. Disorders of platelet adhesion; Bernard-Soulier syndrome • 2. Disorders of platelet secretion; Storage pool deficiency • 3. Disorders of platelet aggregation; Glanzmann thrombasthenia • Acquired • 1. Drugs: Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), dipyridamole, sulfinpyrazone • 2. Renal failure: Uremia • 3. Hematologic malignancies: Myeloproliferative neoplasms and myelodysplastic syndromes
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  Defective adhesion ofplatelets • Two factors are important for adhesion of platelets to subendothelial matrix during normal hemostasis. • One being the platelet membrane glycoprotein complex Ib-IX, which is the receptor for the other factor, i.e. vWF. • Bernard-Soulier (giant platelet) syndrome is an autosomal recessive disorder due to a hereditary deficiency of the platelet membrane glycoprotein complex Ib-IX. • Patients present with purpura, bruising, epistaxis and gingival bleeding during early life. Peripheral smear examination shows mild thrombocytopenia and large platelets
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  Disorders of plateletsecretion • Defect in the secretion may be due to lack of normal storage granules or due to defect in release of granules namely, dense granules or alpha granules. • Storage pool deficiency (SPD) is an autosomal dominant heterogeneous group of disorders in which there is a deficiency of dense granules. • Gray platelet syndrome is due to the lack of α-granule proteins because of which the platelets and megakaryocytes appear gray (pale) on peripheral blood smear
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  Defective platelet aggregation •Glanzmann thrombasthenia is an autosomal recessive disorder. It is due to the deficiency of glycoprotein IIb-IIIa, a protein complex that helps in the formation of “bridges” between platelets by binding fibrinogen. • There is defective aggregation of platelets in response to platelet aggregators like adenosine diphosphate (ADP), collagen, epinephrine or thrombin. • Clinical presentation is in the form of epistaxis and bleeding from gums.
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  Acquired Defects ofPlatelet Function • Drugs: aspirin and other nonsteroidal anti-inflammatory drugs. Metabolism of arachidonic acids requires enzyme cyclooxygenase for the synthesis of platelet aggregator thromboxane A2. • Aspirin is a potent irreversible inhibitor of the enzyme cyclooxygenase and this platelet anti aggregating effect of aspirin is the basis for its use in the prevention of thrombosis in cases of coronary artery disease or cerebrovascular stroke. • The defective aggregation lasts for 7-10 days even at a low dose of 60 mg aspirin. • Renal failure: Uremia produces several abnormalities in platelet function. • Hematologic malignancies: In myeloproliferative neoplasms and myelodysplastic syndromes, platelet dysfunction is due to intrinsic platelet defects.
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  Disseminated intravascular coagulation(DIC) •It’s a complex disorder characterized by both wide spread clotting and bleeding in the Vascular system. • Causes; Sepsis, trauma, cancer and obstetric complication • Pathogenesis; Activation of the coagulation cascade leads to formation of microthrombi in the small blood vessels • Consumption of clotting factors and platelets can lead to bleeding
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  Contn • Bleeding frommultiple site; venipuncture, mucous membranes and internal organs • Thrombosis ; formation of microthrombi can lead to organ dysfuction • Lab abnormalities; prlong PT, aPTT, low platelet count, and elevated D- dimers levels • Treatment; address underlying cause, supportive care including blood transfusion and clotting factors replacement.
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