Chapter 14_2 flashcards
(52 cards)
Immune Thrombocytopenic Purpura (ITP): Definition & Pathophysiology
Autoimmune disorder; autoantibodies (IgG) develop against platelets (often GPIIb/IIIa complex). Platelet-antibody complexes are phagocytosed by macrophages and destroyed by the spleen, leading to thrombocytopenia.
ITP: Epidemiology & Types
Incidence: 66 cases/million/year. Acute ITP: More common in children, often follows viral infection, self-limited. Chronic ITP: More common in adults (peak 20-50 yrs), twice as often in women, may be associated with AIDS or SLE.
ITP: Clinical Presentation & Diagnosis
Signs of bleeding (petechiae, purpura, gum bleeding, epistaxis, abnormal menstrual bleeding). Splenomegaly possible. Diagnosis: Severe thrombocytopenia (<20,000/uL), diagnosis of exclusion (rule out drug-induced, etc.).
ITP: Treatment
Corticosteroids, IV immunoglobulin (IVIg), platelet transfusion (if severe bleeding), immunosuppressive drugs. Splenectomy may be necessary for chronic/refractory cases.
Thrombotic Thrombocytopenic Purpura (TTP): Definition & Pathophysiology
Combination of thrombocytopenia, hemolytic anemia, thrombotic vascular occlusions, fever, neurological abnormalities. Caused by deficiency of/autoantibodies to ADAMTS13 metalloprotease (acts on vWF). Lack of ADAMTS13 -> unmodified vWF -> platelet adhesion & aggregation -> widespread microthrombi.
TTP: Etiology & Associations
Etiology often unclear. Common in HIV infection, pregnant women. Trigger for endothelial damage.
TTP: Classic Pentad of Signs/Symptoms
- Microangiopathic hemolytic anemia (schistocytes on smear).
- Thrombocytopenic purpura.
- Neurological abnormalities (headache, seizures, altered consciousness).
- Fever.
- Renal disease.
TTP: Diagnosis
Clinical pentad. Schistocytes on peripheral smear. Negative direct antiglobulin (Coombs) test. Test for ADAMTS13 activity/antibodies. Differentiate from HUS.
TTP: Treatment & Complications
Treatment: Plasmapheresis (plasma exchange) with fresh frozen plasma (FFP) is mainstay. Corticosteroids. Rituximab (off-label).
Complications: MI, stroke, TIA, miscarriage. High mortality if untreated.
Drug-Induced Thrombocytopenia: General Mechanism & Onset
Many drugs (heparin, antimalarials, sulfonamides most common) can cause antibody-mediated platelet destruction. Typically occurs ~1 week after starting drug or intermittently over longer period (can be 1-2 days post first exposure).
Drug-Induced Thrombocytopenia: Symptoms & Management
Petechial hemorrhages, purpura. Systemic: lightheadedness, chills, fever, nausea, vomiting often precede bleeding. Severe: epistaxis, GI/GU bleeding. Management: Stop causative drug; platelet count usually normalizes in <1 week.
Heparin-Induced Thrombocytopenia (HIT): Unique Feature & Mechanism
Paradoxically associated with increased risk of THROMBOSIS, not just bleeding. Results from development of an antibody to heparin-platelet factor 4 complex, activating platelets and causing aggregation and low platelet count.
HIT: Onset & Treatment
Develops ~5-10 days after heparin (UFH or LMWH) exposure. Thrombi can be arterial or venous. Treatment: Discontinue heparin immediately. Use direct thrombin inhibitors (e.g., argatroban, bivalirudin) or fondaparinux for anticoagulation.
Hemophilia A: Definition & Genetics
Genetic disorder caused by deficiency of Factor VIII. X-linked recessive (primarily affects males; females are carriers).
Hemophilia B (Christmas Disease): Definition & Genetics
Genetic disorder caused by deficiency of Factor IX. X-linked recessive (primarily affects males).
Hemophilia (A & B): Pathophysiology & Clinical Severity
Deficient/dysfunctional coagulation factor -> impaired blood clotting. Severity varies (mild, moderate, severe). Mild: bleeding usually with trauma. Severe: spontaneous bleeding.
Hemophilia: Hallmark Symptom & Common Bleeding Sites
Hallmark: Spontaneous acute hemarthrosis (bleeding into joint space - knee, elbow, ankle common). Other sites: Soft tissue, GI tract, muscles (can cause compartment syndrome), oropharyngeal, CNS (can be fatal).
Hemophilia: Diagnosis
CBC (Hgb/Hct normal or low, platelets normal). PT normal. aPTT prolonged. Specific Factor VIII assay (for Hemophilia A) or Factor IX assay (for Hemophilia B) shows deficiency.
Hemophilia: Treatment
Factor VIII replacement therapy for Hemophilia A. Factor IX replacement for Hemophilia B (recombinant factors preferred to reduce viral transmission risk). Desmopressin (DDAVP) for mild Hemophilia A (stimulates vWF/Factor VIII release). Antifibrinolytic agents (aminocaproic acid, tranexamic acid). Monoclonal antibodies (emicizumab for Hemophilia A with inhibitors).
Essential Thrombocytosis (ET) / Primary Thrombocythemia: Definition
Rare, chronic bone marrow disorder; megakaryocyte proliferation increases circulating platelet count (>600,000/uL). Increased risk of clotting OR bleeding (if platelets dysfunctional).
ET: Epidemiology & Etiology/Pathophysiology
Median age at diagnosis 60 yrs. No known etiology. Gene mutations in ~50% JAK2; others CALR, MPL. Dysfunctional platelets can cause bleeding or hyperaggregation leading to clots.
ET: Clinical Presentation
~25-33% asymptomatic. Symptomatic: Clots (stroke, MI, DVT, PE) or bleeding. Neurological: headache, paresthesias. Erythromelalgia (burning, erythema of ischemic fingers/toes). TIAs. Complications in pregnancy.
ET: Diagnosis
CBC: unexplained high platelet count (may also have high WBC/RBC). Bone marrow biopsy: megakaryocytic hyperplasia. PT/aPTT usually normal. Elevated uric acid in 25%. Imaging for splenomegaly.
ET: Treatment
Inhibit megakaryocyte maturation/platelet production: Hydroxyurea, anagrelide, interferon alfa, busulfan, ruxolitinib (kinase inhibitor). Low-dose aspirin for microvascular clotting. Plateletpheresis in emergencies.
