Krafts IHO Week 6 Flashcards
1
Q
Pro-Clotting: Blood Vessels Constricts
A
blood loss decreases, platelets and factors meet
2
Q
Pro-Clotting: Platelets form a plug
A
proteins are exposed, platelets adhese, granules release contents, platelets aggregate, phospholipids are exposed
3
Q
Pro-Clotting:fibrin seals up plug
A
tissue factor is exposed, cascade begins, cascade makes fibrin, fibrin solidifies plug
4
Q
Anti-Clotting: 1. Cascade Inhibition
A
TFPI, ATIII, Protein C,S
5
Q
Anti-Clotting: 2. Clot Lysis
A
t-PA, plasmin
6
Q
alpha granule
A
fibrinogen, vWF
7
Q
delta granule
A
serotonin, ADP, Ca2+
8
Q
Membrane Phospholipids
A
activate coag factors
9
Q
Membrane GP 1a
A
binds collagen
10
Q
Membrane GP 1b
A
binds vWF
11
Q
Membrane GP IIb-IIIa
A
binds fibrinogen
12
Q
Where does tissue factor (TF) come from?
A
‘hidden’ cells exposed during injury, microparticles floating in blood, endothelial cells and monocytes (during inflammation)
13
Q
Closure Time
A
-alternative to bleeding time, platelet function analyzer measures how quickly platelets occlude small holes (in vitro bleeding time), better than the bleeding time at detecting aspirin related bleeding and von Willebrand ds
14
Q
causes of increased PT
A
decreased VII, X, V, II, I or coumadin, heparin and DIC
15
Q
When to order a PT?
A
NEVER (order an INR instead which is a corrected PT)
16
Q
Why do you order an INR?
A
to assess liver function, monitor Coumadin therapy, dx DIC and to assess pre-op status
17
Q
PTT (partial thromboplastin time)
A
plasma + phospholipid, measures intrinsic pathway, APTT=same thing
18
Q
PTT increased in
A
hemophilia A, hemophilia B, DIC, heparin, inhibitors
19
Q
When should you a PTT?
A
- investigate a hx of abnormal bleeding time 2. monitor heparin therapy 3. dx DIC 4. dx an antiphospholipid antibody 5. assess pre-op status
20
Q
Thrombin Time
A
Plasma + thrombin, measures conversion of fibrinogen to fibrin, bypasses intrinsic and extrinsic pathways
21
Q
TT increased in
A
low fibrinogen and high FDPs
22
Q
When to order a TT?
A
when the PTT is prolonged and you want to r/o a fibrinogen problem (rare)
23
Q
PTT Mixing Study
A
pooled plasma + patient plasma + phospholipid
24
Q
If PTT corrects
A
something is missing=factor deficiency
25
If PTT doesn't correct
inhibitor present
26
When should you order a mixing study?
when PTT is prolonged and TT is normal
27
Fibrin Degradation Product Assay
Measures FDPs (fibrin degradation products), very sensitive
28
FDPs increased
thrombi, minor clotting
29
When to order an FDP assay?
not to rule in a clot, but to RULE OUT a clot
30
Hereditary Bleeding Disorders
von Willebrand disease, Hemophilia A and B, Hereditary platelet disorder
31
Acquired bleeding disorders
DIC, ITP, TTP/HUS
32
Platelet Bleeding
superficial (skin), petechiae, spontaneous
33
Factor Bleeding
Deep (joints), big bleeds, trauma
34
most common hereditary bleeding disorder, autosomal dominant, vW factor decreased (or abnormal), variable severity
Von Willebrand Disease
35
huge multimeric protein, made by megs and endothelial cells, glues platelets to endothelium, carries factor VIII, decreased or abnormal vW disease
von Willebrand Factor
36
Type 1 Von Willebrand Disease
70%, decreased vWF
37
Type 2 Von Willebrand
25%, abnormal vWF
38
Type 3 Von Willebrand
5%, no vWF
39
mucosal bleeding in most patients, deep joint bleeding in severe cases
Von Willebrand Disease
40
Lab Tests in VW Disease
prolonged bleeding time, PTT prolonged that corrects with mixing study, normal INR, vWF level decreased (normal in type 2), platelet aggregration studies abnormal
41
Tx of VW Ds: DDAVP
raises VIII and vWF levels
42
Tx of VW Ds: Cryoprecipitate
contains vWF and VIII
43
Tx of VW Ds
Factor VIII
44
most common factor deficiency, X-linked recessive in most cases (30% are random mutations), factor VIII level decreased, variable amount of 'factor' bleeding
Hemophilia A
45
Sx of Hemophilia A
severity depends on amount of VIII, typical 'factor' bleeding (deep joint bleeding and prolonged bleeding after dental work), rarely, mucosal hemorrhage
46
Lab Tests in Hemophilia A
INR, TT, platelet count, bleeding time all normal, PTT prolonged that corrects with mixing study, abnormal factor VIII assays, DNA studies abnormal
47
Tx of Hemophilia A
DDAVP and Factor VIII
48
factor IX level decreased, much less common than hemophilia A, same inheritance pattern, same clinical and laboratory findings
Hemophilia B
49
Rare Factor Deficiencies
XI deficiency (bleeding after trauma) and XIII deficiency (severe neonatal bleeding)
50
abnormal Ib, abnormal adhesion, big platelets, severe bleeding
Bernard-Soulier Syndrome
51
No IIb-IIIa, no aggregation,severe bleeding
Glanzmann Thrombasthenia
52
No alpha granules, big empty platelets, mild bleeding
Gray Platelet Syndrome
53
no delta granules, can be part of a syndrome (Chediak-Higashi)
delta granule deficiency
54
lots of underlying disorders, something triggers coagulation to cause thrombosis, platelets and factors get used up and cause bleeding, microangiopathic hemolytic anemia
Disseminated Intravascular Coagulation
55
Causes of DIC: Dumpers
obstetric complications, adenocarcinoma, acute promyelocytic leukemia
56
Causes of DIC: Rippers
bacterial sepsis, trauma, burns, vasculitis
57
malignancy, OB complications, sepsis, trauma
DIC
58
Sx of DIC
Insidious or fulminant, multi-system ds, thrombosis and/or bleeding
59
Lab Tests in DIC
INR, PTT and TT prolonged; FDPS increased, Fibrinogens decreased
60
Tx of DIC
tx underlying disorder, support with blood products
61
antiplatelet antibodies, acute vs chronic, dx of exclusion, steroids or splenectomy
Idiopathic Thrombocytopenic Purpura
62
autoantibodies to GP IIb-IIIa or Ib, bind to platelets, splenic macrophages eat platelets
Pathogenesis of ITP
63
Chronic ITP
adult women, primary or secondary, insidious (nose bleeds, easy bruising), danger (bleeding into the brain)
64
Acute ITP
children, abrupt; follows viral illness, usually self-limiting, may become chronic
65
Lab Tests in ITP
signs of platelet destruction (thrombocytopenia, normal/increased megakaryocytes, big platelets), normal INR/PTT, no specific dx test
66
5 Other Causes of Thrombocytopenia
aplastic anemia, bone marrow transplant, big spleen, consuptive processes (DIC, TTP, HUS), drugs
67
TX of ITP
glucocorticoids, splenectomy, IV Ig
68
all have thrombi, thrombocytopenia and MAHA, include TTP and HUS, can be hard to distinguish from TTP and HUS, something triggers platelet activation, different from DIC
Thrombotic Microangiopathies
69
Pentad (MAHA, thrombocytopenia, fever, neurologic defects, renal failure), deficiency of ADAMTS13, big vWF multimers trap platelets, plasmapheresis or plasma infusions
Thrombotic Thrombocytopenic Purpura
70
Just-released vWF is unusaually large (UL), UL vWF causes platelet aggregation, ADAMTS13 cleaves UL vWF into less active bits and TTP is dt ADATS13 deficiency
Pathogenesis of TTP
71
Clinical Findings in TTP
hematuria and jaundice (MAHA), bleeding and bruising (thrombocytopenia), fever, bizarre behavior (neurologic deficits), decreased urine output (renal failure)
72
Tx of TTP
acquired: plasmapheresis, hereditary: plasma infusions
73
MAHA and thrombocytopenia, epidemic (e.coli) v non-epidemic, toxin or damages endothelium, tx supportively
Hemolytic Uremic Syndrome
74
Pathogenesis of HUS-Epidemic
E.coli O157:H7 (raw hamburger), makes nasty toxin, injures endothelial cells
75
Pathogenesis of HUS-Non epidemic
defect in complement factor H, inherited or acquired, does does this activate platelets
76
Epidemic HUS Clinical findings
children, elderly, blood y diarrhea and then renal failure and is fatal in 5% of cases
77
Non-epidemic HUS Clinical findings
renal failure, relapsing-remitting course, fatal in 50% of cases
78
Tx of HUS
supportive care, dialysis, NOT abx as may increase toxin release
79
Thrombosis Risk Factors
Endothelial damage (atherosclerosis-HTN, hyperlipidemia, obesity, smoking) and Stasis (immobilization, varicose veins, cardiac dysfunction) and Hypercoagulability (trauma/surgery, carcinoma, estrogen/postpartum, thrombotic disorders)
80
Hereditary Thrombotic Disorders
Factor V Leiden, ATIII deficiency, protein C deficiency, protein S deficiency, factor II gene mutation, homocysteinemia
81
Acquired Thrombotic Disorders
Antiphopholipid Ab
82
most common cause of unexplained thromboses, point mutation in factor V gene (can't be cleaved by protein C), factor V can't be turned off, need genetic testing for dx
Factor V Leiden
83
Risk of Clot with Factor V Leiden
Heterozygotes 7x, homozygotes 80x, normal risk is 1-2 pts per 1000 per year
84
a natural anticoagulant (inhibits IIa, VIIa, IXa and XIa), potentiated by heparin, lots of gene mutations exist, very rare
Antithrombin III Deficiency
85
Mutated Gene in ATIII
produces LESS ATIII, rara avis (1%), can't do genetic testing
86
Risk of Getting a Clot in ATIII
homo: can't survive, hetero half get clots, heparin won't work and antithrombin concentrates required
87
natural anticoagulants, fibrinolytic and anti-inflammatory, wafarin induced skin necrosis, purpura fulminans, rare
Protein C Deficiency
88
natural anticoagulants, wafarin induced skin necrosis, super rare
Protein S Deficiency
89
Describe Protein C
anticoagulant (inactivates Va and VIIIa), fibrinolytic (promotes t-PA action) and anti-inflammatory (keeps cytokines low)
90
Risk of Clot with Protein C Deficiency
hetero: 7x normal
91
What does coumadin inhibit?
II, VII, IX, X and C and S
92
thrombotic state and vascular injury to skin necrosis, associated with protein C and S deficiency and sepsis, tx may include administering protein C
Purpura Fulminans
93
mutated gene makes too MUCH prothrombin, rare in non-caucasians, 5% of caucasians, clot risk 2-20 times normal
Factor II (prothrombin) Gene Mutation
94
Too much homocysteine leads to
thromboses
95
amino acid, made from methionine, maintains myelin and converts dietary folate
Homocysteine
96
rare metabolic disorder, deficient trans-sulphuration enzyme, increase homocytsteine in blood and urine, increase thrombosis, premature atherosclerosis
Homocysteinuria
97
MTHFR gene mutation or B12/folate deficiency
Homocysteinemia
98
Negatives of Homocysteine
toxic to endothelium (ROS) and interferes with NO (a vasodilator and antithromboitc)
99
Risk of thrombosis with heterozygous homocysteinemia
venous 2.5x and arterial 10x
100
autoantibodies against phospholipids, falsely prolong INR, may cause thromboses
Antiphospholipid Antibodies
101
anticardiolipin antibodies, lupus anticoagulants, antibodies against other molecules
IgG antibodies to phospholipids
102
recurrent thrombosis, recurrent spontaneous abortions, increased risk of stroke, pulmonary HTN, renal failure
antiphospholipid antibody syndrome
103
How to detect Antiphospholipid Antibodies
1. PTT 2. if prolonged order PTT mixing study 3. if normal, antibody may still be present and need to order fancy tests
