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35 Cards in this Set
- Front
- Back
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What is the normal physiology of platelets? Production and Number?
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Normally made in the bone marrow from progenitor cells known as megakaryocytes
Lifespan: 10 days Count: between 150,000 and 450,000 mm^3 |
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What are the 3 steps of platelet plug formation?
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*Adhesion, Aggregation, and Secretion*
Adhesion: platelets stick to injured vessel wall Aggregation: platelets stick to each other via fibrinogen bridges Secretion: platelets release granular contents and potentiate clotting |
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What are the symptoms of platelet dysfunction?
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Platelet hypofunction: the same as defects in primary hemostasis: epistaxis, gum bleeding, bruising, heavy menses, petechiae -- mucocutaneous bleeding; "oozing and bruising"
Abnormal platelet activation: arterial occlusion-- strokes/MI's/gangrenous limbs (if in peripheral arteries) |
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What are the major platelet quantitative disorders?
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Thrombocytopenia: too few platelets
Thrombocytosis/Thrombocythemia: too many platelets |
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What is pseudothrombocytopenia, and why should it be considered when evaluating thrombocytopenia?
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"platelet clumping"
certain patients' platelets clump when blood is added to EDTA test tubes --> platelet count is artificially low and there is no bleeding consequence in this scenario because platelets are normal in vivo |
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What are the ranges to consider for platelet counts?
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150,000-100,000 completely clinically silent
100,000-50,000 no symptoms, can have abdominal surgery, not CNS surgery 50,000-20,000 first symptoms: oozing and bruising 20,000-10,000 usually need to treat, maybe not transfuse <10,000 risk for spontaneous ICH -- needs immediate treatment |
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What are the three broad categories for causes of thrombocytopenia?
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*Underproduction*
*Peripheral Destruction* *Splenic Sequestration* |
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What can cause underproduction of platelets?
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Marrow failure (myelodysplasia, aplastic anemia, vit def)
Marrow infiltration (tumor, granulomatous, leukemia) Marrow toxins (chemo, radiation, alcohol) |
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What can cause peripheral destruction of platelets?
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Non-immune mechanisms (DIC, TTP)
Immune mechanisms: antibody-mediated -- can be provoked by drugs, associated with HIV or autoimmune disease, or idiopathic |
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What is DIC?
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Disseminated Intravascular Coagulation
A process characterized by abnormal activation of coagulation, generation of too much thrombin, consumption of clotting factors, destruction of platelets, and activation of fibrinolysis |
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How is DIC diagnosed?
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Elevated PT
Low platelets Low/falling fibrinogen Elevated D-dimers or fibrin degradation products Schistocytes on peripheral smear (most cases) |
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What are the etiologies of DIC?
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Gram-negative sepsis, severe burns, obstetircal disasters, certain leukemias, shock, insect or snake venoms
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How do you treat DIC?
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Treat the underlying cause!
Supportive measures: transfusion of platelets, clotting factors (FFP), fibrinogen (cryoprecipitate) |
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What is TTP?
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Thrombotic Thrombocytopenic Purpura
A process characterized by abnormal activation of platelets and endothelial cells, with von Willebrand factor and fibrin deposition in the microvasculature, and peripheral destruction of platelets and RBCs |
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How is TTP diagnosed?
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*The Pentad*
Microangiopathic Hemolytic Anemia (MAHA): elevated LDH and bilirubin; schistocytes Low platelets Fever Neurologic manifestations: HA, confusion, seizures, coma Renal manifestations: hematuria, proteinuria, inc. BUN |
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What are the etiologies of TTP?
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Sporadic
Drugs: quinine, cyclosporine, tacrolimus, ticlopidine Increased incidence with pregnancy or AIDS |
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What is the pathophysiology associated with sporadic cases of TTP?
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Sporadic cases- antibody against protease ADAMTS-13, which cleaves the ultra-large MW multimers of vWF --> vWF are really long, stick together/clump because ADAMTS-13 cannot cleave them
The accumulation of vWF multimers --> abnormal platelet activation |
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What is the progression and prognosis of TTP?
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>90% fatal without therapy
80-90% survive with therapy one-third of patients relapse within 10 years, most within 1 month of diagnosis |
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How do you treat TTP?
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Remove all inciting factors
PLEX: Plasma Exchange (sometimes with corticosteroids) Secondary measures: splenectomy, vincristine, Rituximub AVOID platelet transfusions --- they fuel the fire! |
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What is HUS?
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Hemolytic Uremic Syndrome
Fewer neurologic sequelae, more renal & GI manifestations than TTP |
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What is the etiology and treatment for HUS?
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Usually precipitated by diarrheal illness, esp. E Coli O157:H7 or Shigella (Shiga toxin binds to endothelial cells in kidney -> cell death)
May respond less well to plasma exchange "NC State Fair disease" |
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What are the mechanisms of drugs/immune-mediated thrombycytopenia?
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Directly stimulting anti-platelet antibody production
A hapten mechanism "Innocent bystander" phenomenon |
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Which drugs can induce thrombocytopenia?
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Beta-lactam antibiotics
Trimethoprim-sulfamethoxazole, other sulfa drugs Quinine/quinidine Heparin |
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What occurs in heparin-induced thrombocytopenia? What should you do if platelets fall after heparin is started?
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After 7-10 days after starting heparin, platelets fall by at least 30-50%
Caused by antibodies against teh complex of heparin/PF4 *If platlets fall on heparin, STOP heparin immediately* Can lead to thrombosis in some patients (antibodies -> platelet activation |
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What is ITP? How is it diagnosed?
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Immune Thrombocytopenic Purpura
Diagnosis of exclusion --- there is NO diagnostic test Megakaryocytes should be present in the marrow |
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What provokes ITP in children? How is it treated?
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Usually by viral illness
Spontaneously remits No specific therapy usually required |
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How is ITP treated in adults?
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Specific therapy required if platelet count is <30K-50K or if patient is bleeding
Corticosteroids If platelet count is <10K or if patient is bleeding -> more rapid therapy --> IVIg and steroids Secondary: splenectomy, Rituximab |
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What is splenic sequestration?
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Displacement of platelets from peripheral circulation into splenic pool
Splenic enlargement from any cause can lead to sequestration |
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What are the indications for platelet transfusions?
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To raise the platelet count prophylactically to prevent bleeding or to treat acute bleeding in patients with low PLT counts
*Blood banks will not release platelets if the patient's platelet count is ABOVE a certain number |
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With which types of thrombocytopenia should platelets be transfused?
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ITP - only if severe bleeding
NOT with TTP Splenic sequestration - only if severe bleeding Hypo-production - tends to be a numerical trigger (7K-10K) to transfuse |
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What are the two major categories of thrombocytosis?
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Primary - i.e. myeloproliferative syndromes
Secondary - i.e. reactive |
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What are the characteristics and main diseases associated with primary thrombocytosis?
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Platelets are both hyper- and hypo-functional
May lead to thrombosis and/or bleeding Diseases include: Essential Thrombocythemia, Polycythemia Vera, CML and myelofibrosis |
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What are the characteristics and main diseases associated with secondary thrombocytosis? How is it treated?
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Reactive
Causes include: inflammation, infection, bleeding, iron deficiency Usually does not lead to thrombosis Treat the underlying cause |
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How are qualitative platelet disorders diagnosed?
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Prolonged bleeding time --- PFA-100 (in vitro)
Follow-up by platelet aggregation studies PT/PTT/TCT should be all normal |
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What is the differential diagnosis for qualitative platelet disorders?
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Congenital: Glanzmann's thrombaesthenia (defect in IIb/IIIa on platelet surface; Bernard-Soulier (defect in Ib/IX on platelet surface
Acquired: uremia, myeloproliferative diseases, ASA, NSAIDs, ginkgo, garlic, Vit E |
