Disorders of clotting DSA Flashcards
possible bleeding disorder- characteristics
- hemorrhage after surgery or trauma
- systemic dz?
- drug ingestions
- FH
suspected coagulopathy- lab testing?
- platelet count
- bleeding time
- PT, aPTT
- thrombin time
possible clotting disorder- characteristics
- venous thromboembolism (>90% of cases)
- DVT or PE
- FH of thrombosis
- first episode of thrombosis in young adulthood
congenital disorders of coagulation
- Hemophilia A (def of factor 8)
- hemophilia B (def of factor 9)
- von willebran dz
- factor 11 def
- less common heritable disorders of coagulation
Hemophilia A and B- essentials of dx
(X-linked recessive)
- recurrent hemarthroses and arthropathy
- risk of development of inhibitory ab’s to factor 8 or 9
- older pts- infection with HIV or HCV in the 1980s due to exposure of contaminated blood products
Hemophilia A and B- sx and signs
severe- factor 8 activity < 1%- early childhood- bleeding into joints, soft tissues
- mild (activity > 5%)- spontaneous bleeding is rare, but occurs after surgery, trauma
- moderate (activity 1-5%)
Hemophilia A and B- tx
- recombinant factor 8 or 9 products
- mild bleeding- DDAVP
Von Willebrand disease- essentials of diagnosis
- most common inherited bleeding disorder
- VWf binds platelets to subendo surfaces, aggregates platelets, and prolongs the half-life of factor 8
Von Willebrand disease- types
- 1- quantitative abnormality- 80% of pts
- 2- qualitative defect- dec binding to factor 8 or to platelets
- 3- rare- severe bleeding in infancy
Von willebrand disease- signs and sx
-type 1- mild/moderate bleeding
-2- moderate to severe
3- severe
von willebrand dz- tx
- DDAVP
- vWF product
factor 9 deficiency
- autosomal recessive
- Ashkenazi Jews
- mild bleeding
less common heritable disorders of coagulation
- def of clotting factors 2, 5, 7, 10
- autosomal recessive
Acquired disorders of coagulation
- acquired ab’s to factor 8, 2, or 5
- vit K def
- coagulopathy of liver dz
- warfarin ingestion
- DIC
- heparin/fondaparinux/direct-acting oral anticoagulant use
- lupus anticoagulants
Vit K def- caused by?
- def dietary intake, malabs, or dec production by intestinal bacteria
- assists in the coag factors 2, 7, 9, 10
- prolonged PT
Vit K def- tx
-vit K1 (phytonadione)
Coagulopathy of liver dz
- dec syn of clotting factors- 2, 5, 7, 9
- prolonged PT
- normal factor 5 level indicates vit K def!!!
- also def of fibrinogen
Severe DIC due to acute promyelocytic leukemia
- dec in the activity of clotting factors
- aPTT and PT prolonged
- platelets and fibrinogen levels are reduced
Acquired factor 8 inhibitor
- extensive soft-tissue ecchymoses, hematomas, mucosal bleeding
- aPTT prolonged
- Bethesda assay- titer of the inhibtor
thrombotic disorders- most common?
- factor V leiden
- prothrombin gene mutation
primary hypercoagulable states
- Antithrombin III def
- protein C def
- protein S def
- act protein C resistance (factor V leiden)
- prothrombin gene mutation
antithrombin III def- path
- leads to inc fibrin accum and propensity to thrombosis!!!
- antithrombin is a inhibitor of thrombin and other act coag factors- its def leads to unreg protease activity and fibrin formation
antithrombin III- in who? types?
- in 1% of pts with venous thromboembolism
- 2.5% of pts with recurrent thrombosis
- type 1- quantitative deficiency
- type 2- fxnally defective
- type 3- dysfxnal protein (due to specific point mutations)
- autosomal dominant!
- most pts affected are heterozygous
protein C def- path
- unregulated fibrin generation b/c of impaired inactivation of factors 8a and Va
- type 1- quantitative def
- type 2- abnormalities in prot C act or fxn
- autosomal dominant!!!
- most pts affected are heterozygotes
protein S def- path
- principal cofactor of activated protein C (APC)
- its def mimics that of protein C- loss of regulation of fibrin generation by impaired inactivation of factors 8a and 5a
Activated protein C resistance (Factor V Leiden)
- mutation is in 3-8% of white populations of European ancestry
- causes APC resistance!!
- point mutation in the gene for factor V
Prothrombin Gene mutation (prothrombin G20210A)
- assoc with elevated levels of prothrombin and an inc risk of venous thrombosis
- more common in white populations
primary hypercoagulable states- clinical manifestations
venous thromboembolic (VTE) complications!
- DVT and PE- most common!
- recurrent pregnancy loss
- VTE usually occurs in early adulthood
venous vs arterial thromboses
-venous- unusual sites- superficial thrombophlebitis and mesenteric and cerebral venous thrombosis
-arterial thrombosis involving the
coronary, cerebrovascular, and peripheral circulations is not linked to any primary hypercoag states!
secondary hypercoagulable states
- hyperhomocysteinemia
- malignant dz
- myeloproliferative neoplasms and PNH
- antiphospholipid syndrome
- pregnancy, oral contraceptives, hormone replacement therapy
- systemic infl
- postop state, immoblization, trauma
malignant dz- what type of cancer?
- thrombotoc complications in cancer pts depends in part on the type of malignant dz
- hypercoagulability most prominent in pancreatic cancer, adenocarcinoma of GI tract, lung, ovarian cancer, hematologic malignant neoplasms
myeloproliferative neoplasms and PNH- clinical?
- thrombosis and bleeding!!
- PV- inc whole blood viscosity- thrombosis
- hepatic v thrombosis and other intra-abd venous thromboses- assoc with these!!
Antiphospholipid syndrome- characterized by? clinical?
- characterized by- venous and arterial thrombosis, recurrent spontaneous pregnancy loss, thrombocytopenia, and neuropsychiatric manifestations
- autoab’s bind to phospholipid-protein complexes
- positive tests that detect diff plasma antiphospholipid-protein ab’s!!
- DVT and PE most common
