Ch. 4 - Hemostasis and Related Disorders Flashcards
1
Q
What is goal of primary hemostasis?
A
formation of weak platelet plug
2
Q
What is the goal of secondary hemostasis?
A
stabilization of platelet plug via coagulation cascade
3
Q
What is step 1 of primary hemostasis?
A
transient vasoconstriction of blood vessels
4
Q
What 2 things is transient vasoconstriction mediated by?
A
1) neural stimulation
2) endothelin release from endothelial cells
5
Q
What is step 2 of primary hemostasis?
A
platelet adhesion to surface of disrupted vessel by binding to GPIb receptor of vWF (which is bound to subendothelial collagen)
6
Q
What is vWF derived from?
A
Weibel-Palade bodies of endothelial cells and a-granules of platelets
7
Q
What is step 3 of primary hemostasis?
A
platelet degranulation and release of ADP and TXA1
8
Q
What is the function of ADP from platelet degranulation?
A
released by platelet dense granules and promotes exposure of GPIIb/IIIa receptor on platelets
9
Q
What is the function of TXA2 from platelet degranulation?
A
promotes platelet aggregation (derived from cyclooxygenase)
10
Q
What is step 4 of primary hemostasis?
A
platelet aggregation via GPIIb/IIIa using fibrinogen to form a weak platelet plug
11
Q
What are the common clinical signs of primary hemostasis disorders?
A
- Sx of mucosal bleeding
- epistaxis, hemoptysis, GI bleeding, hematuria, and menorrhagia
- intracranial bleeding with severe thrombocytopenia
- Sx of skin bleeding
- petechiae, ecchymosis, purpura
- easy burising
12
Q
What is petechiae a sign of?
A
thrombocytopenia - quantitative disorder
13
Q
What is a normal platelet count?
A
150-400K/uL
14
Q
What is a normal bleeding time?
A
2-7 min
15
Q
What is the pathogenesis of immune thrombocytopenia purpura?
A
autoimmune production of IgG against plaetlet antigens (i.e. GPIIb/IIIa)
16
Q
What produces the antibodies in ITP and how does that lead to thrombocytopenia?
A
plasma cells in spleen - Ab-bound platelets are consumed by splenic macrophages, resulting in thrombocytopenia
17
Q
What happens in acute ITP?
A
seen in children weeks after viral or immunization; self limited
18
Q
What happens in chronic ITP?
A
seen in women of child bearing age; may be primary or secondary
19
Q
What is a secondary association of ITP?
A
SLE
20
Q
Why may pregnant women see transient ITP in their offspring?
A
anti-platelet IgG can cross the placenta
21
Q
What are the labs of ITP?
A
- low platelet count, <50K/ul
- normal PT/PTT
- increased megakaryocytes on bone marrow biopsy
22
Q
What is the Tx of ITP?
A
corticosteroids
-children respond well; adults may relaps
23
Q
How can platelet count be raised in symptomatic bleeding of ITP?
A
IVIG administration - short-lived
24
Q
What is eliminated in refractory cases of ITP requiring splenectomy?
A
source of antibody and site of destruction
25
What is the basis of microangiopathic hemolytic anemia?
pathologic formation of platelet microthrombi in small vessels that shears RBCs causing schistocytes
26
What is consumed in the formation of microthrombi?
platelets
27
What kind of cell looks like a dented helmet?
schistocyte - sheared RBC
28
What is the defect in TTP?
deficiency of ADAMTS13 which cleaves vWF multimers into smaller monomers for degradation --> large, uncleaveed multimers lead to abnormal platelet adhesion
29
Who is the classic pt of TTP?
adult female who produces Ab against ADMTS13
30
What is HUS due to?
endothelial damage by drugs or infection resulting in platelet microthrombi
31
What bug leads to HUS?
E. coli O157:H7 with verotoxin which damages endothelial cells
32
Who gets E. coli O157:H7?
children eating undercooked beef
33
What are the clinical findings of TTP and HUS?
- skin and mucosal bleeding
- microangiopathic hemolytic anemia
- fever
- renal insufficiency
- CNS abnormality
34
What are the predominant problems in HUS vs. TTP?
HUS: renal insufficiency
TTP: CNS abnormality
35
What are the lab findings in HUS and TTP?
- thrombocytopenia with increased bleeding time
- normal PT/PTT
- anemia with schistocytes
- increased megakaryocytes on bone marrow biopsy
36
What are the Tx of HUS and TTP
plasmapheresis and corticosteroids, particularly in TTP
37
What is the defect in Bernard-Soulier syndrome?
genetic GP1b deficiency --> platelet adhesion is impaired b/c can't bind vWF
-blood smear shows mild thrombocytopenia with enlarged platelets
38
What is a good way to remember enlarged platelets in Bernard-Soulier?
Bernard-Soulier --> "Big Suckers"
39
What is the defect in Glanzmann hrombasthenia?
genetic defect in GIIb/IIIa which impairs platelet aggregation
40
How does ASA impair platelet aggregation?
it irreversibly inactivates cyclooxygenase which prevents formation of TXA2
41
How does uremia disrupt platelet function?
impairs adhesion and aggregation
42
What is the goal of secondary hemostasis?
stabilize the weak plug via development of crosslinked fibrin by thrombin
43
What does activation of coagulation cascade require?
1. exposure to activating substance
2. phospholipid surface from platelet surface
3. Ca2+ from dense core granules of platelets
44
What are clinical features of secondary hemostasis?
- deep tissue bleeding into muscle and joints
| - rebleeding after surgical procedures
45
How is the extrinsic pathway activated?
tissue thromboplastin activates factor VII
46
How is the intrinsic pathway activated?
subendothelial collagen activates factor XII
47
What factors are in the common pathway?
X, V, II, and I
48
What measures intrinsic pathway?
PTT (activated by TT)
49
What measures extrinsic pathway?
PT (activated by SEC)
50
What is Hemophilia A?
genetic FVIII deficiency, XLR (or new mutation)
51
What are the lab findings of Hemphilia A?
-increased PTT, normal PT
-decreased FVIII
-normal platelet count and bleeding count
Tx: recombinant FVIII
52
What is coagulation factor inhibitor?
acquired Ab against a coagulation factor resulting in impaired factor function; anti-FVIII is most common
53
How do you distinguish coagulation factor inhibitor from hemophilia A?
- PTT does not correct upon mixing normal plasma in pt's pkasma (mixing study) d/t inhibitor (Ab binds to normal plasma)
- PTT does correct in hemophilia A
54
What is vWF disease?
genetic deficiency in vWF (most commonly AD) - results in problem with platelet adhesion
55
How do pts with vWF disease present?
mild mucosal and skin bleeding
56
What are the lab findings of vWF disease?
- increased bleeding time
- increased PTT (vWF needed for FVIII), normal PT
- abnormal ristocetin test* (no aggregation of platelets)
57
What is the Tx of vWF deficiency?
desmopression: increases vWF release from Weibel-Palade bodies of endothelial cells
58
What happens in Vitamin K deficiency?
disrupts function of multiple coagulation factors: II, VII, IX, X, and protein C & S (lack of gamma carboxylation and activation)
59
What activates Vitamin K?
epoxide reductase in liver
60
Who does Vitamin K deficiency occur in?
newborns, long-term antibiotic therapy, and malabsorption
61
How does liver failure lead to coagulation deficiency and you measure effect of liver failure on coagulation?
- decreased production of coag factors and decreased activation of vitamin K by epoxide reductase
- liver failure monitored using PT
62
how does large volume transfusion affect secondary hemostasis?
dilutes coagulation factors and results in a relative deficiency
63
What happens in heparin-induced thrombocytopenia?
heparin forms a complex with platelet factor 4 and makes IgG autoAbs which consume platelets made by the spleen and can lead to thrombosis
64
What are the 2 problems that arise with DIC?
1) widespread microthrombi that result in ischemia and infarction
2) consumption of platelets and coag factors that result in bleeding, esp IV sites and mucosal surfaces
65
What are 5 risk factors for DIC?
1) obstetric complication
2) sepsis
3) adenocarcinoma
4) acute promyelocytic leukemia
5) rattlesnake bite
66
What are the lab findings of DIC?
- decreased platelet count
- increased PT/PTT
- decreased fibrinogen
- microangiopathic hemolytic anemia (schistocytes)
- elevated fibrin split prpoducts (D-dimer)*
67
What is D-dimer?
the product of fibrin split products (best screening test for DIC)
68
What is the Tx of DIC?
blood transfusion and cryoprecipitate
69
What converts plasminogen --> plasmin
tPa
70
What does plasmin do?
1) cleaves cross-linked fibrin and serum fibrinogen
2) destroys coag factors
3) blocks platelet aggregation
71
What inactivates plasmin?
a2-antiplasmin
72
What are disorders of fibrinolysis d/t?
plasmin overactivity
73
What are two examples of plasmin overactivity?
1) radical prostatectomy - release of urokinase activates plasmin
2) liver cirrhosis - reduced production of a2-antiplasmin
74
How do pts with plasmin overactivity present?
increased bleeding that resembles DIC
75
What are the lab findings of fibrinolysis disorders?
- increased PT/PTT
- increased bleeding time with NORMAL platelet count
- increased fibrinogen split products WITHOUT D-dimer (no fibrin clots, just overactivity of plasmin)
76
How do you treat fibrinolysis disorders?
aminocaproic acid - blocks activation of plasminogen
77
What are 3 causes of endothelial damage?
1) atherosclerosis
2) vasculitis
3) elevated levels of homocystine
78
What is a thrombosis characterized by?
1) lines of Zahn (alternating lines of RBCs and fibrin)
2) attachment to vessel wall
* both features distinguish thrombus from postmortem clot
79
How do thrombi form in aneurysms?
balloon-like dilatation of blood vessel can lead to turbulence of blood flow
80
What do endothelial cells produce to block platelet aggregation?
PGI2, NO, and tPA
81
What do endothelial cells produce to block anticoagulation?
heparin-like molecule which binds to anti-thrombin III
82
What are the functions of tPA produced by endothelial cells?
1) cleaves fibrin and serum fibrinogen
2) destorys coagulation factors
3) blocks platelet aggregation
83
What does thrombomodulin produced by endothelial cells do?
redirects thrombin to activate protein C, which inactivates factors V and VIII
84
How is methionine formed?
THF-M --> Vit B-M --> homocysteine --> methionine
85
How does Vit B/folate deficiency lead to endothelial damage?
elevated levels of homocysteine damage endothelium
86
What are the Sx of cystathionine beta synthase deficiency?
vessel thrombosis, MR, lens dislocation and long slender fingers
87
What is defective in Protein C or S deficiency?
hypercoagulable state: FV and FVIII overactive
88
What is the pathology of warfarin skin necrosis in presence of Protein C/S deficiency?
factors 2, 7, 9, 10, C, and S are inactivated, but C and S are inactivated first leading to hypercoagulable skin leading to warfarin skin necrosis
89
What is Factor V Leiden?
mutated form of FV that lacks cleavage deactivation by proteins C and S --> hypercoagulable state
90
What happens to PT in pts with ATIII deficiency who are given heparin?
PTT does not rise with standard heparin dosing
91
How are oral contraceptives associated with hypercoagulable state?
estrogen induces increased production of coagulation factors
92
What is characteristic of atherosclerotic embolus?
cholesterol clefts
93
What is the pathology of fat embolus?
associated with bone fractures and soft tissue trauma and presents with dyspnea and petechiae on skin overlying chest
94
Where is gas embolus seen?
decompression sckness - presents with joint and muscle pain (bends) and respiratory Sx (chokes)
95
What is Caisson disease?
chronic gas emboli - multifocal ischemic necrosis of bone
96
How does amniotic fluid embolus present?
shortness of breath, neuro Sx, and DIC
| *characterized by squamous cells and keratin debris
97
How does amniotic fluid embolus lead to DIC?
amniotic fluid contains tissue thromboplastin
98
Why is PE most often clinically silent?
1) lung has dual blood supply
| 2) embolus is usually small and self-resolves
99
When does pulmonary infarction occur d/t PE?
obstruction of large- or medium-sized artery with pre-existing cardiopulmonary compromise
-only 10% of PE cause infarction
100
What tests is useful for PE
spiral CT - vascular filling defect in lung
- LE Doppler US to detect DVT
- elevated infarct
101
What does PE reveal on gross exam?
hemorrhagic wedge-shaped infarct
102
What is a saddle embolus?
embolus that blocks both L and R plumonary artery or with significant occlusion of a large pulmonary artery
-death is d/t electromechanical dissociation
103
What gives rise to systemic embolism?
thromboembolus that most commonly arises in the L heart and occludes flow to organs, most commonly LE
