platelet disorders Flashcards
platelet disorders: common manifestations, general causes, complications
either caused by a quantitative or a qualitative defect in platelets.
cause mucosal bleeding, microhemorrhage, epistaxis, petechiae, increased bleeding time. petechiae suggest lowered platelet numbers.
feared complication: bleeding into the brain.
immune thrombocytopenia: platelet count, bleeding time, pathology, bone marrow biopsy, types, treatment
most common cause of thrombocytopenia.
the spleen makes IgG antibodies against platelet antigens, which bind platelets. platelet-antibody complexes are removed by splenic macrophages.
platelet count down, BT up.
types: acute vs. chronic. acute seen in kids weeks after a viral infection and resolves spontaneously.
chronic seen in adults and may be primary or secondary (SLE). may cause short lived thrombocytopenia in offspring (IgG crosses placenta).
incr. megakaryocytes in bone marrow.
normal PT/PTT.
treatment: steroids (work in kids, sometimes in adults but often relapse), IVIG is short lived but may raise platelets in symptomatic bleeding, splenectomy in refractory cases
bernard-soulier syndrome: pathology, labs
defect in platelet plug formation. decreased Gp1b prevents platelets from binding to vWF. platelet count is low, bleeding time high, platelets are large.
qualitative defect
glanzmann thrombobasthenia:
defect in platelet plug formation because of low levels of GpIIb/IIIa. this causes a defect in platelet-platelet binding. platelet count is NORMAL but bleeding time is high.
qualitative defect.
microangiopathic hemolytic anemia: what is it? clinical manifestations? labs?
pathologic formation of platelet microthrombi in small vessels. platelets are consumed in the formation of microthrombi. RBCs are sheared as they cross microthrombi, leading to hemolytic anemia with schistocytes. seen in TTP and HUS. bptj cam cause skin and mucosal bleeding, fever.
thrombocytopenic purupra: pathogenesis, labs, symptoms, treatment
reduced levels of ADAMTS13, an enzyme that cleaves vWF multimers into smaller monomers for eventual degradation. large multimers lead to abnormal platelet adhesion, resulting in microthrombi. decreased ADAMTS13 is usually seen in adult women because of an acquired autoantibody.
labs: incr bleeding time, thrombocytopenia, normal PT/PTT, anemia with schistocytes, incr. megakaryocytes on bone marrow biopsy.
symptoms: may cause CNS abnormalities as microthrombi involve brain vessels; fever, renal symptoms, thrombocytopenia, microangiopathic hemolytic anemia.
tx: plasmapheresis and corticosteroids
HUS
endothelial damage by drugs or infection, usually in kids with E. coli O157:H7 dysentery. E coli verotoxin damages endothelial cells, which causes platelet microthrombi.
see skin and mucosal bleeds, microangiopathic hemolytic anemia, fever, renal insufficiency (maybe CNS defects).
uremia and bleeding disorders
disrupts platelet function- both adhesion and aggregation are impaired
DIC: symptoms, labs, treatment
pathologic activation of the coagulation cascade, usually secondary to another cause. microthrombi result in ischemia and infarction. consumption of platelet and factors results in bleeding, esp. from IV sites and mucosal surfaces.
labs: decr. platelet, incr. PT/PTT (important!), decr. fibrinogen, elevated fibrin split products (esp. D-dimer). elevated D-dimer is the best screeing test for DIC. this is derived from splitting of cross-linked fibrin, not splitting of fibrinogen (entire coag cascade has been activated. recall that fibrinogen is replaced with fibrin). tx: address underlying cause and transfuse blood products and cryoprecipitate (coag factors).
causes of DIC
obstetric complication- tissue thromboplastin in amniotic fluid activates coagulation; sepsis, esp. with E coli or N meningitidis- endotoxins from bacterial wall and cytokines (TNF and IL-1) induce endothelial cells to make tissue factor), adenocarcinoma (mucin activates coagulation), acute promyelocytic leukemia (primary granules), rattlesnake bite.
heparin-induced thrombocytopenia
platelet destruction that arises secondary to heparin. fragments of destroyed platelets activate remaining platelets, causing thrombosis
disorders of fibrinolysis
plasmin overreactivity- excessive cleavage of serum fibrinogen. may be seen after radical prostatectomy (release of urokinase activtes plasmin), or cirrhosis of liver (reduced production of alpha2-antiplasmin). presents with bleeding that resembles DIC. incr. PT and PTT (plasmin destroys clotting factors), incr. bleeding time with normal platelet count (plasmin prevents platelet aggregation), incr. fibrinogen split products without D-dimers.
give AMINOCAPROIC ACID- blocks activation of plasminogen
hemophilia, including diagnostics
genetic factor VIII (A) or IX (B) deficiency. X linked recessive, but can arise from a new mutation w/o any family hx. deep tissue, joint, and postsurgical bleeds. incr. PTT, normal PT. normal platelet count and bleeding time.
coagulation factor inhibitor, including diagnostics
acquired antibody against a coagulation factor resulting in impaired factor function. anti-FVIII most common. similar to hemophilia A in presentation. PTT does NOT correct uppon mixing normal plasma with patien’ts plasma due to inhibitor (PTT does correct with hemophilia A).
vikamin K deficiency
disrupts function of multiple coagulation factors (II, VII, IX, X and C and S). seen in newborns (no GI colonization of bacteria that synthesize vitamin K_. long-term antibiotic therapy (disrupts vitamin K producing bacteria in the GI tract), fat malabsorption
