PLATELETS: Clotting disorders

[liveonearth]

NORMAL PLT
--count is 140,000-440,000
--varies by menstrual cycle
--decreases in preg near term
--increases with inflam
--platelet lifespan 7-10 days
--disorders include increased/decreased numbers, malfunction: failure to clot/overclotting

GENERAL S/SX OF PLT DISORDER
--unexplained epistaxis
--menorrhagia
--prolonged bleeds after minor trauma
--easy bruisng
--petechiae
--unexplained gingival bleeds
--hx of bleeds (family or individual)
--nsaids intake
--hematuria
--GI bleeds
--hemoptysis

GENERAL DIAGNOSTICS:
**CBC: thrombocytopenia/thrombocytosis dx'd from counts only
--suspect platelet dysfunction if CBC, IRN, and PTT are normal
**COAGULATION STUDIES: INR/PT
--extrinsic and common pathways (VII, X, V), prothrombin, fibrinogen
--INR is standardized to help with Warfarin dosing
--in vivo coagulation is mostly extrinsic.
**COAGULATION STUDIES: PTT
--intrinsic and common pathways (XII, XI, IX, VIII, X, V)
--prolonged by heparin, warfarin/coumadin
--prolonged by auto-ab's to factor VIII (hemophilia)
--factors must be at least 70% deficient to see prolonged PT/PTT
**BLEEDING TIME TEST = controversial, used more by naturopaths than conventional docs, multifactorial but useful for helping pt w/ longterm maintenance of clotting level, 6-8 mins optimal, 2-10 normal.

THROMBOCYTOPENIA = low platelets
--easy minor bleeding under 50,000
--5,000 mb more serious
--some pts with less than 10,000 mb Asx
--Dx: CBC, coag studies, PB smear. Suspect platelet dysfunction if CBC, INR and PTT are normal.
--ETIO (acquired: aspirin), NSAIDS, MOA: prevents production of Thromboxane A2
--effect of NSAIDS lasts 5-7 days
--ETIO: SPLENIC SEQUESTRATION (PLT under 30,000) dt: cirrhosis, myelofibrosis, myeloid metaplasia

HEREDITARY INTRINSIC PLATELET DISORDERS
--three types:
--1) poor activation
--2) Glanzmann's Thromboasthenia (rare, autosomal recessive, severe mucosal bleeds dt no aggregation)
--3) Bernard-Soulier syndrome (also rare, auto-recess, LARGE platelets, impaired adhesion, severe bleeds)
--Dx: platelet aggregation tests

ITP = IDIOPATHIC THROMBOCYTOPENIC PURPURA = autoimmune w/ platelet destruction
--mb triggered by viral infx in kids, chronic in adults
--S/Sx: peteichiae, mucosal bleeding, splenomegaly for kids
--Dx: unexplained thrombocytopenia, low PLT otherwise normal CBC,
--Dx: BM biopsy: normal/increased megakaryocytes
ITP = IDIOPATHIC THROMBOCYTOPENIC PURPURA
--purpura = dz causing subcu bleeding
--Most common Thrombocytopenia cause in children
--Peak onset between ages 2 to 4 years
--IgG Antibody develops against platelet membrane antigen
--Acute follows Viral Exanthem or viral Infection, occurs in otherwise healthy patients
--Chronic Insidious onset in patient with immune disorder more common in teenage girls
--S/Sx: Purpura, Mild Splenomegaly in 5 to 10% of cases
--Absent signs: fever, lethargy, pallor or weight loss, bone or joint pain, LAD, hepatomegaly
--LABs: Platelet Count drops rapidly
--Tx: Corticosteroids, Splenectomy in refractory cases
--splenectomy: Safe and effective, mb preferred in younger patients, Gadenstatter (2002) Am J Surg 184:606


THROMBOTIC THROMBOCYTOPENI PUPURA = microangiopathic TT
--platelets destroyed by fibrin in small vessels-->thrombi in multi organs
--Grouped with HUS (HUS is more in children, more in kidneys)
--ETIO: ADAMTS13 enzyme deficient in plasma, hemorrhagic colitis from E. Coli 0157 or some shigella, preg, drugs (quinine, cyclosporine, mitomycin C), idiopathic
--S/Sx: fever, organ ischemia sx. Dx: suspect w/ anemia, thrombocytopenia, and sx.
--LABS: US, PB smear, Retic ct, serum LDH, renal fx, serum bilirubin, Coomb's test
--DX SUGGESTED BY: anemia, RBC fragments, hemolysis (falling HGB, polychomasia, elevated retics, negative Coombs)

HEMOLITIC UREMIC SYNDROME = TTP in kids
--characterized by microangiopathic hemolytic anemia, acute renal failure and a low platelet count
--dt EHEC or shigella (caused by shiga toxin)
--usu spontaneously remits
--untx mb fatal
--usu only one incidence

VON WILLEBRAND'S DZ = PROBLEM WITH VW FACTOR (VWF) => doesn't clot well
--VWF promotes platelet adhesion by binding platelets to endothelium of vascular sys
--Hereditary, impaired syn of VWF->long bleed time, mild-severe factor 8 deficiency
--Autosomal dominant inheritance
--S/Sx: usu mild-mod, skin & mucosal bleeds, easy bruise, menorrhagia, prolonged bleeds after surgery
--Dx: suspect in those w/ fam hx or personal hx of bleeding dz, coag tests mb normal (normal INR/PT, slighly prolonged PTT), normal PLT count
--DX DEFINITIVE: test for plasma VWF antigen, VWF fx, and Factor 8
--Dx: VWF antigen mb 40% below normal in HEALTHY peerson with TYPE O BLOOD. Beware of ASA (aspirin)