Hemostasis and related disorders Flashcards
1
Q
Describe primary hemostasis
A
- vWB factor (released from Weibel-Palade bodies of endothelial cells and alpa-granules of platelets) binds to exposed collagen.
- GP1b receptor of platelets binds vWF inducing degranulation
- ADP is released stimulating expression of GP2b3a
- TXA2 is released stimulating platelet aggregation
- GP2b3a receptors bind fibrinogen forming weak platelet plug that is then stabilized by coagulation cascade
2
Q
Name the primary hemostasis disorders
A
- Immune thrombocytopenic purpura (ITP)
- Microangiopathic hemolytic anemias (thrombic thrombocytic purpura (TTP) and hemolytic uremic syndrome (HUS))
- Bernard-soulier and Glanzmann thrombasthenia (qualitative platelet disorders)
3
Q
Who gets Immune thrombocytopenic purpura (ITP)?
A
- Most common cause of thrombocytopenia in children and adults
- Acute, normally self limiting following infection in children
- Chronic, appears in women of child bearing age (sometimes secondary to SLE), can be passed to fetus, temporary.
4
Q
What are the lab findings in Immune thrombocytopenic purpura (ITP)?
A
- Decreased platelet count <50 k
- Normal PT/PTT
- Increased megakaryocytes on bone marrow biopsy
5
Q
What is the treatment for Immune thrombocytopenic purpura (ITP)?
A
- Corticosteroids effective in children, adults normally relapse.
- IVIG for bleeding normally short lived.
- Spenectomy (refractory cases).
6
Q
What causes thrombic thrombocytic purpura (TTP)?
A
- Decrease in ADAMTS13 (an enzyme that cleaves vWF multimers for eventual degradation) normally due to autoantibodies, commonly seen in women.
- vWF multimer leads to abnormal platelet aggregation and microthrombi formation–> Microangiopathic hemolytic anemia.
7
Q
What is the cause of HUS?
A
- Caused by endothelial damage by drugs or infection (verotoxin)
- Commonly caused by E. Coli O157 H7 in children
8
Q
What are the clinical findings of TTP and HUS?
A
- Microangiopathic hemolytic anemia
- Skin and mucosal bleeding and fever
- Renal insufficiency (HUS)
- CNS defects (TTP)
9
Q
What are the laboratory findings for MHA?
A
- Thrombocytopenia with increased bleeding time
- Normal PT/PTT
- Anemia with schistocytes
- Increased megakaryocytes on bone marrow biopsy
10
Q
What is the treatment for MHA?
A
- Plasmapheresis and corticosteroids particularly in TTP
11
Q
What is the cause of Bernard-soulier and Glanzmann thrombasthenia?
A
- Bernard-soulier - Genetic GP1b deficiency
- Glanzmann thrombasthenia - Genetic GP2b3a deficiency
12
Q
How does secondary hemostasis stabilize the weak platelet plug?
A
- Coagulation cascade generates thrombin
- Thrombin converts fibrinogen to fibrin
- Fibrin cross linking stabilizes the platelet thrombus
13
Q
What activates secondary hemostasis? and which pathway is activated?
A
- Tissue factor (released by endothelial cells)–> factor 7 (extrinsic pathway, TP)
- Subendothelial collagen–> factor 12 (intrinsic pathway, TTP)
- Phospholipid suface of platelets and Ca
14
Q
What causes hemophilia A?
A
- Factor 8 deficiency (X-linked recessive, and de novo mutation)
15
Q
How does a patient with hemophilia A present and what are the laboratory findings?
A
- Deep tissue, joint and post surgical bleeding
- Increased PTT, normal PT
- Decreased factor 8
- Normal platelets and bleeding time
16
Q
What is the treatment for hemophilia A?
A
- Recombinant factor 8
17
Q
What is hemophilia B?
A
- Factor 9 deficiency
- Resembles hemophilia A
18
Q
What is coagulation factor inhibitor? What is the most common factor? and How is it distinguished from hemophilia A?
A
- Developed autoantibody against coagulation factor.
- Most commonly factor 8
- PTT does not correct when mixed with normal plasma
19
Q
What is Von Willebrand disease?
A
- Deficiency in vWF
- Most common inherited coagulation disorder
- Many variants, most common of which is autosomal dominant reduction in vWF
20
Q
How does patient present with VWD?
A
- Mild mucosal and skin bleeding
- Deep tissue, joint and post surgical bleeding typically not seen
21
Q
What are the lab findings for VWD?
A
- Increased bleeding time
- Increased PTT, normal PT (vWF stabilizes factor 8)
- Abnormal rictocetin test - Induces vWF GP1b binding and platelet aggregation
22
Q
What is the treatment for VWD?
A
- Desmopressin (ADH analog) - increases vWF release for Weibel-palade bodies and alpha granules
23
Q
How does vitamin K effect secondary hemostasis?
A
- Epoxide reductase released by the liver actives vitamin K–> vitamin K gamma
- Vitamin K gamma activates –> factors 2, 7, 9, 10, C, S
24
Q
When does vitamin K deficiency occur?
A
- New borns - due to the absence of bacteria that produce vit K. Given vit K injection at birth to prevent hemorrhagic disease of the new born.
- Malabsorption, fat soluble vitamin
- Long-term antibiotic therapy, destruction of gut bacteria
25
What are other causes of secondary hemostasis and why do they occur?
- Liver disease - decreased production of coagulation factors and epoxide reductase (no activation of vitamin K)
- Large volume transfusions - dilution leads to relative deficiency
26
How does heparin induced thrombocytopenia occur?
- Heparin therapy induces platelet destruction causing the release of cytokines causing the activation of the remaining platelets--> thrombus
27
What are the causes of DIC?
- Obstetric complications --> Tissue thromboplastin from fetus into maternal blood--> coagulation
- Sepsis (E. Coli, N. menengitidis) - Endotoxin and cytokines (IL-1 and TNF) --> TF production
- Adenocarcinoma --> Mucin --> coagulation
- Acute promyelocytic leukemia --> Primary granules actives coagulation
- Rattlesnake bite --> venom activates coagulation
28
What are the laboratory findings for DIC?
- Decrease platelet count
- Increase PT/PTT
- Decrease fibrinogen
- Increase fibrin split products
- Microangiopathic hemolytic anemia
29
What is the treatment for DIC?
- Blood products and cryoprecipitate (contains coagulation factors)
30
What is the normal mechanism of fibrinolysis?
- Tissue plasminogen activator converts plasminogen to plasmin which cleaves fibrin and fribrinogen, destroys coagulation factors and blocks platelet aggregation
- Alpha-2 antiplasmin breaks down plasmin
31
What causes fibrinolysis disorders and what are some examples?
- Plasmin overactivity
- Radical prostatectomy- urokinase release
- Cirrhosis of the liver- decreased production of alph-2 antiplasmin
32
What are the laboratory findings for disorders of fibrinolysis?
- Increased PT/PTT
- Increased bleeding time with no increase in platelets
- Increased fibrinogen split products with no D-dimers
33
How do patients present with disorders of fibrinolysis?
- Increased bleeding resembling DIC
34
How are disorders of fibrinolysis treated?
- Aminocaproic acid which blocks activation of plasminogen
35
How is a thrombus differentiated from postmortem clot?
- Lines of Zahn
| - Attachment to vessel wall
36
What are the three major risk factors in thrombus formation?
- Disruption in blood flow
- Endothelial cell damage
- Hypercoagulable state
37
What are examples of disruption in normal blood flow?
- Immobilization
- Cardiac wall disfunction
- Aneurysm
38
By what mechanisms do endothelial cells prevent coagulation?
- Block subendothelial collagen
- PGI2 and NO: vasodilation and platelet inhibition
- Secrete heparin like molecule: augment antithrombin 3 --> inactivates thrombin and coagulation factors
- Secrete tissue plasminogen activator
- Secretes thrombomodulin--> redirects thrombin to activate protein C --> inactivvation of 5 and 8
39
What are some contributing factors to endothelial damage?
- B12, folate and cystathionine beta synthase (CBS) deficiency --> increased levels of homocysteine
40
What factors contribute to hypercoagulabe state?
- Protein C or S deficiency
- Factor 5 Leiden
- Prothrombin 20210A
- Antithrombin 3 deficiency
- Birthcontrol
41
What causes immune thrombocytopenic purpura?
- IgG antibodies against platelet antigens (GP1b, GP2b/3a)
