Thrombostasis Flashcards
Describe in 4 steps the process of primary hemostasis
- transient vasoconstriction - endothelin
- adhesion: GpIb to vWF to collagen on endothelium
- degranulation:
-ADP –> exposure of GPIIB/IIIa
-TXA2 by COX - promotes aggregation - aggregation:
GPIIb/IIIa to fibrinogen
What are the clinical findings of primary hemostasis disorders?
mucosal and skin bleeding:
- GI, epistaxis, hemoptysis, hematuria, menorrhagia
- petechiae
- severe: intracranial hemorrhage
What is the most common cause of thrombocytopenia in both children and adults?
immune thrombocytopenic purpura
What drug can cause induced thrombocytopenia via igG
heparin
What is the cause of TTP?
dec ADMNTS13 - enzyme that normally cleaves vWF
-due to acquired autoantibody
What bacteria is infamous for causing HUS?
Ecoli - verotoxin damages endothelial cells
Is renal insufficiency or CNS insufficiency more common in TTP? HUS?
TTP: CNS
HUS: Renal
What is the effect on PT/PTT in HUS and TTP?
NONE
-no effect on coagulation cascade
What is wiskott aldrich syndrome?
affected boys have small platelets, eczema, immunodeficiency
What antigen can cause neonatal alloimmune thrombocytopenia?
HPA1a
Name the genetic defect and result:
-Bernard soulier syndrome
GPIb deficiency
- adhesion is impaired
- mild thrombocytopenia, enlarged platelets
Big Suckers
Name the genetic defect and result:
-glanzman thrombasthenia
GPIIB/IIIa deficiency
- aggregation is impaired
- normal platelet count
Who does purpura simplex affect?
women during menses
-purpuric spots of dermis
What are four causes of thrombocytosis?
- iron deficiency anemia
- splenectomy
- cancer
- chronic inflammatory disorder
What is the goal of secondary hemostasis?
- stabilizes the weak platelet plug
- thrombin converts fibrinogen –> fibrin
What are some clinical features of secondary hemostasis disorders?
- deep tissue bleeding into muscle and joints
- rebleeding after surgical procedures
What pathways does PT/PTT measure?
PT: extrinsic and common
PTT: intrinsic and common
Describe the intrinsic pathway?
subendothelial collagen –> 12–>11–>9–>8
What drug affects the intrinsic pathway?
heparin
Describe the extrinsic pathway?
tissue thromboplastin–> 7
What drug affects the extrinsic pathway?
coumadin
Describe the common pathway
fibrinogen –> 5, 2, 1
What factor is deficient in hemophilia A? what is the result
factor VIII
- inc PTT
- deep tissue bleeding
What factor is deficient in christmas or hemophilia B
factor IX
What is the most common acquired autoantibody against a coagulation factor
vIII and then vWF
in a mixing study, would PTT be corrected for patients with hemophilia A or patients with a coagulation inhibitor autoantibody?
ONLY hemophilia A
-coagulation inhibitor would block factor VIII still and PTT would remain inc
What is the most common inherited coagulation disorder?
vWF deficiency - autosomal dominant
in vWF disease, is PT , PTT, or neither increased?
PTT is increased
- vWF is needed to stabilize factor VIII
- intrinsic pathway
What test diagnoses vWF disease?
Ristocetin test - induces platelet agglutination - lack of agglutination diagnoses vWF disease
How is vWF disease treated?
desmopressin - induces vWF release from weibel palade bodies
What factors does vitamin K deficiency disrupt
2, 7, 9, 10 protein C and S
Describe the pathology of DIC
procoagulant TF is released after injury and inappropriately activates factor 12
What are five situations in which DIC is likely?
- obstretic complication - thromboplastin in amniotic fluid
- Ecoli or N meningitis
- adenocarcinoma - mucin
- APL - primary granules
- rattle snake bite
What are some lab findings in DIC
- dec platelet
- inc PT and PTT - consumption of clotting factors
- dec fibrinogen
- elevated fibrin split products - D-dimer
- THIS result is most sensitive - shistocytes
What are two conditions that can cause disorders of fibrinolysis and why?
- radical prostatectomy - urokinase - actvates plasmin
2. cirrhosis of the liver - reduced alpha 2 antiplasmin
What are the lab findings in a fibrinolysis disorder?
- inc PT/PTT
- inc bleeding time
- inc fibrinogen split products - NOT d dimer
what are some things that are released when endothelial cells are damaged that lead to thrombosis?
- NO and prostacyclin
- heparin like molecules - block anti thrombin III
- TPA
- thrombomodulin
When heparin is initially given which factors are relatively deficient?
protein c and s
What do protein C and S normally inactivate?
factor V and VIII - amplifying factors
What is the most common cause of inherited hypercoaguable state?
factor V leiden - lacks cleavage site for deactivation by protein C and S
What lab test indicates antiIII deficiency?
PTT does not rise with heparin
