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Platelet Disease


Examples of platelet disease Acute Thrombocytopenia; HIT; ITP; TTP; HUS
Causes of thrombocytopenia (decrease in plt numbers) Decreased prodn (BM prob); inc destn (meds, immune mediated, DIC); Sequestration (Splenomegaly)
ITP diagnosis is: one of exclusion (ie, notable for what is not present)
ITP findings Neg FH/SH/PMH. Labs = acute thrombocytopenia; all else normal. Bruising, petechiae, gingival bleeding, hemorrhagic bullae in kids
ITP tx Immunosuppression (prednisone 1mg/kg/day; rituximab; cyclophosphamide ). Immune modulation (IVIg, splenectomy). Stimulate platelet production (eltrombopag, romiplostin)
2 types of HIT 1: transient decrease. 2: immune mediated (significant)
HIT mechanism Heparin combines w/PF4; this plus Abs -> platelet activation -> limb or life threatening thrombosis
HIT PMHx On heparin 4-10 days; Inflammation/necrosis?; limb asymmetry? ; Cool/pulseless extremities?
HIT tx Stop all heparin products (inc hep lines & flushes & LMWHs); prompt tx w/alt. anti-coagulation: Direct Thrombin Inhibitor (Argatroban, Lepirudin, Bivalirudin); Fondaparinux (synthetic anti-coagulant); warfarin after plt normal; w/alt anticoag; 6-12 wks
Increase in ultra-high molecular weight multimers of von Willebrand factor (2/2 deficiency vWF proteolytic enzyme) = TTP
Effects of TTP Intra-vascular platelet aggregation; systemic manifestations (CNS, Renal, Cardiac, Hematologic)
H&P for TTP mental status changes; Sx/Sx related to end-organ damage and those of acute & idiopathic thrombocytopenia
TTP tx Emergent large-volume plasma plasmapheresis; RBCs and fresh plasma returned to patient. Possible prednisone & antiplatelet tx
Platelet release involves: Release of PF3 (Platelet factor 3); intracellular Ca (enhances further activation); thromboxane A2
Adult ITP is usually: chronic (as opposed to children, no viral infxn).
Most common drug causing ITP Heparin
TTP clinical findings Pentad: MAHA; thrombocytopenia; CNS abnormalities; fever; renal dysfunction
HUS: mental status changes? No
HUS findings Thrombocytopenia
Dx similar to TTP but without neuro symptoms HUS
AutoAb to ADAMTS13 seen in: TTP
HUS prognosis Self-limiting in kids. 40% mortality in adults; CKD in 80%
Platelet aggregation abnormal with ristocetin, which corrects with the addition of normal platelets, in: Bernard-Soulier Syndrome
HIT involves: IgG antibody to Platelet Factor 4
Confirm HIT with: Serotonin Release Assay
Most common drug induced form of thrombocytopenia HIT
HIT type I Non-immune mediated: 100K platelets, no thrombosis (dc heparin)
HIT type II Immune mediated: 30K platelets, thrombosis risk (require dc heparin, Rx direct thrombin inhibitors & warfarin)
HUS tx D+ HUS: supportive; NO PLTS, NO ABX. Plasmapheresis & FFP
IgG antibody to PF4: seen in: HIT (both art & venous thrombosis)
Microangiopathic hemolytic anemia & thrombocytopenia without an identifiable cause = TTP (also often see neuro sxs)
anemia with schistocytes, thrombocytopenia & renal dysfunction in the absence of other causes of coagulopathy = HUS
DIC vs HUS: dx DIC low fibrinogen; HUS normal fibrinogen
Anagrelide may be used for: P vera; thrombocytosis
Bleeding disorder clinical findings: platelet vs coagulopathy plt: mucosa & skin; petechiae in low plt (NOT plt dysfn); coag: skin & mx; spont hemarthrosis in severe hemophilia
most common cause of abnormal bleeding: thrombocytopenia
HUS vs TTP HUS: no neuro sxs, more renal > TTP
Causes of decreased platelet function: membrane defects Glanzmann Thrombasthenia; Bernard-Soulier
Causes of decreased platelet function: Pathway Defects Arachidonic Pathway Defect
Causes of decreased platelet function: medications Aspirin/Clopidogrel use
Causes of decreased platelet function: acquired disease MDS
Diseases causing ITP SLE, CLL, virus (HIV/Hep C)
von W defect is in: platelet adhesion only
HIT occurs when? 4-10 days post heparin infusion
Adult ITP epidemiology Peak = 20-50 y.o. (2-4 yo in kids). F:M = 2:1
ITP etiology Acquired autoimmune. Isolated thrombocytopenia. Autoantibody binds to platelet membrane antigen -> bound to splenic macrophages & destroyed in spleen -> low platelets 2/2 splenic sequestration & accelerated platelet destruction
Created by: Abarnard