Disorders of Thrombosis and Hemostasis CIS Flashcards
primary hemostasis
- platelet adhesion- dep on glycoproteins on platelet surface and mediated by VwF
- act platelets have storage granules and secrete factors (ADP, serotonin)- which recruit other platelets
- formation of a platelet plug
secondary hemostasis
- serum coag factors- development of fibrin latticework which braces the platelet plug
- also recruit platelets
most common cause of bleeding?
-thrombocytopenia
lab tests for bleeding disorders
- CBC- for plt count
- PT- 2, 5, 7, 10, fibrinogen def
- PTT- 8, 9, 11, 12 def
- PS examination- morphology of formed elements
- plt aggregation studies
PT
- extrinsic system
- 10-13 seconds
- prolonged- 2, 5, 7, 10, fibrinogen def
- prolonged in pts taking warfarin or dicoumarol
PTT
- intrinsic system
- 25-40 seconds
- prolonged- 8, 9, 11, 12 def
- prolonged in pts taking heparin
platelet aggregation studies
- determine qualitative platelet defects
- abnormal in pts taking aspirin or NSAIDS
- Vonwillebrand disease, storage pool dz, Bernard-soulier syndrome
in pts with petechiae and thrombocytopenia- potential cause?
medications!
DIC
- complicaiton of medical, surgical, and obstetrical situations
- coag systems are act- results in initial thrombosis stage
- plts and clotting factors depleted- bleeding!
DIC- tx
-correction of underlying disorder!!
Thrombotic thrombocytopenic purpura (TTP)
-thrombocytopenic purpura, microangiopathic hemolytic anemia, neuro signs, renal dysfxn, and fever
(if add renal failure- HUS!!)
TTP- signs, sx’s
- microangiopathic anemia- schistocytes (RBC fragments)
- hyaline thrombi- occlude capillaries
TTP- 2 forms
- hereditary- mutation of ADAMTS13 gene (von willebrand factor-cleaving protease)
- acquired- autoab’s to ADAMTS13
TTP- tx
- treat the cause
- plasmapheresis- life saving in 100%
vonWillebrand disease
- dec platelet adhesion to vascular endothelium (usually mediated by vWF)
- dec or absent production of vWF
vonWillebrand disease- lab, tx
- platelet aggregation tests are normal- esp to ristocetin!!!
- tx- cryoprecipitate- replaces vWF
- DDAVP- causes release of vWF from endothelium
Factor Deficiencies
- Hemophilia A and B
- vonwillebrand disease
- vit K-dep fafctors
Hemophilia A
- X-linked recessive
- def of Factor 8
- mild (6-25% normal activity); moderate (1-5%); severe (<1%)
Hemophilia A- clinical features
- easy bleeding, bruisability
- hematomas- bleeding into soft tissues and muscles
- hemarthroses
- risk for bleeding after surgery
Hemophilia B
- def of factor 9
- tx- replacement of factor 9 for hemorrhage or prophylactically for surgery
Deficiency of Vit-K dep factors
- bleeding/hemorrhage
- prolonged PT
- def of 2, 7, 9, 10, protein C and S
Hereditary Hemorrhagic Telangiectasia
(Osler-Weber-Rendu syndrome)
- only endothelial syndrome assoc with hemostatic complications
- thinning of vessels walls, AV malformations, aneurysmal dilatations thruout body
- autosomal dominant
- defect in gene coding for endoglin (CD 105)- a membrane glycoprotein expressed on endo cells
Hereditary Hemorrhagic Telangiectasia- clinical features
- telangiectasias- skin, mucous membranes, visceral tissues
- bleeding- to mild/inapparent trauma; epistaxis most common sx
- usually benign
Hereditary Hemorrhagic Telangiectasia- tx
-surgery and laser photoablation of telangiectasias
liver dz coagulopathy- treat with?
fresh frozen plasma has clotting factors in it)
thrombotic disorders
- antithrombin III def
- protein C and S def
- factor V leiden syndrome
- prothrombin 20210
- antiphospholipid syndrome
- superficial venous thrombosis
AT-III def- clincial
- LE thrombophlebitis and DVT, venous insuff, chronic leg ulcers
- 50% affected have DVT or PE by age 30
- inc risk for DVT in pregnant women
- dx- AT-III levels < 50% of normal activity
AT-III Def- tx
- prophylactic tx- anticoagulants
- pts with DVT- heparin (high doses required)
- AT-III replacement therapy- pts with DVT who dont respond to heparin
Def of protein C and S- clinical, tx
(vit K-dep)
- C- inact factor 5 and 8
- S- cofactor for protein C
- clinical- similar to AT-III Def
- warfarin- dec risk of thromboembolic dz
def of protein C and S- most common cause of hypercoagulable state from def of these proteins?
- initiation of warfarin therapy!
- C and S depleted prior to other factors- temporary inc in coagulability
Factor V Leiden
- abnormality of factor V at binding site for act protein C (cant be inact)
- heterozygotes- inc risk for thromboembolic dz
- homozygotes- high risk for thromboembolism
Factor V Leiden- tx
- no prior episodes- monitor, DVT prophylaxis
- prior episodes- lifelong anticoagulation
Prothrombin 20210
- inc activity for prothrombin, and inability to de-act prothrombin
- very high risk of thrombosis
- tx- same as factor V leiden
Antiphospholipid syndrome- terms
- anticardiolipin ab
- lupus anticoagulant (misnomer)
- false positive VDRL ab
Antiphospholipid syndrome- assoc features
- thromboembolic
- miscarriage
- thrombocytopenia
- cerebral ischemia and recurrent stroke (in young pts_
- UBO (unidentified bright objects) on MRI scans
- CT dz- in 50%
- prolonged PTT- fails to correct with mixing studies
- valvular HD- in some
- CAD- in some
Antiphospholipid syndrome- dx- 3 tests
- prolonged PTT
- lack of correction in mixing studies using normal plasma
- neutralization of inhibitor with excess phospholipid
- DRVVT (dilute russell viper venom time) may be more specific than PTT test- used for lupus anticoagulant variety!
Antiphospholipid syndrome- tx
- no benefit for anticoagulation in those with no hx of thromboembolisms
- if have hx- lifelong anticoagulation- but most do mult positive tests over a 3-12 month period for dx!
- anticoagulation during pregnancy- SC heparin
- hydroxychloroquine- reduce thromboembolism in pts with APS and SLE
hypercoagulability panel
-factor V leiden, prothrombin gene mutation, protein C and S
