Week 10 - clotting Flashcards
1
Q
What is primary vs secondary vs tertiary hemostasis?
A
Primary - platelet plug
Secondary - fibrin clot
Tertiary - clot stabilization
2
Q
What are some potential DDx of primary hemostatic issues?
A
Decreased or dysfunctional platelets (liver disease, CKD), vascular disorders (Ehlers-Danlos, HIT)
3
Q
What are some potential DDx of secondary hemostatic issues?
A
hereditary clotting factor deficiencies, acquired deficiencies, DIC
4
Q
Compare petechiae vs purpura vs ecchymosis
A
Petechia: <2mm
Purpura: purple-coloured spots 3-5mm
Ecchymoses: aka bruising
5
Q
What are the intrinsic, extrinsic, and common coagulation factors?
A
Intrinsic: F7
Extrinsic: F12,11,9,8
Common: F10,5,2,1
6
Q
Name 6 different blood products available to patients
A
- blood transufsion
- platelet transfusion
- plasma transfusion
- fibrinogen concentrate
- cryoprecipitate
- prothrombin complex concentrate
7
Q
When do you give a blood transfusion?
A
Hb<70, massive bleeding, cardiac ischemia
8
Q
When do you give platelet transfusions?
A
platelets <10
9
Q
When are platelet transfusions contraindicated?
A
In those with TTP or HIT
10
Q
What is in plasma transfusions?
A
coagulation factors and fibrinogen
11
Q
When is fibrinogen concentrate indicated?
A
In those with fibrinogen deficiency
12
Q
What is in cryoprecipitate?
A
Factors 8, 13, fibrinogen, and VWF
13
Q
When is PCC indicated? What is in it?
A
Antidote for warfarin- contains Vitamin K dependent factors
14
Q
What are the 4 zones of platelets?
A
Peripheral zone, sol-gel zone, organelle zone, membrane system
15
Q
Describe platelet peripheral zone
A
Surface membranes with glycoproteins for adhesion
16
Q
Describe platelet sol-gel zone
A
cytoskeleton
17
Q
Describe platelet organelle zone
A
alpha granules containing adhesion proteins (fibrinogen, VWF) and delta granules containing ATP, ADP, Ca
18
Q
What are the 4 steps of hemostasis
A
- arteriolar vasoconstriction
- exposure of ECM and platelet adhesion, aggregation, and activation
- TF release and coagulation cascade
- formation of permanent plug
19
Q
Describe target of aspirin
A
targets COX to decrease production of thromboxane A2 and platelet activation
20
Q
Describe target of Clopidrogel
A
targets P2Y12 receptor to prevent platelet activation
21
Q
Describe target of Abciximab
A
targets glycoproteins to prevent platelet aggregation, also directly inhibit F10a
22
Q
Describe target of heparin
A
enhances plasma protein antithrombin to prevent thrombin generation
23
Q
Which coagulation factors are non-enzymes?
A
5 and 8
24
Q
Compare hemophilia A and B
A
A- factor 8 def
B- factor 9 def
25
Describe role of VWF in clotting
1. recruits platelets (involved in adhesion and aggregation)
2. chaperone for F8 during secondary hemostasis
26
What are the Vit K dependent factors?
2,7,9,10
27
What does the fibrinolytic system do?
Removes and regulates clots
28
Describe fibrinolytic system
tissue plasminogen activator activates plasminogen to plasmin, which targets and degrades fibrins
29
What inhibits tPA?
PAI-1
30
What does fibrin get degraded to?
D-dimers
31
Reasons for isolated elevated PT/INR?
F7 issue: Liver disease, warfarin, Vitamin K deficiency, congenital F7 deficiency
32
Reason for isolated elevated PTT?
Issue with intrinsic pathway: heparin, lupus anticoagulants, severe VWD (F8), congenital F12/11/9/8 deficiency
33
Reason for elevated PT/INR and PTT?
common pathway issue: DIC, severe liver disease, severe Vit K deficiency/warfarin, high dose heparin, new anticoagulants, congenital F10/5/2/1 deficiency
34
What are the next steps if you dont see any differences in PTT or PT/INR?
Look at VWD, factor 8 deficiency, platelet function disorder
35
How do you determine if a factor inhibitor is present?
Mixing study
36
How can types of bleeding be used to distinguish different hemostatic issues?
mucosal bleeds = primary hemostasis
joint/soft tissue bleeds = secondary hemostasis
delayed bleed after injury = tertiary hemostasis
37
What tools are used to distinguish between regular/pathogenic bleeds?
BAT
38
What can caused thrombocytopenia?
decreased marrow production, increased destruction, sequestration
39
What can cause a dysfunctional platelet plug?
IPD, VWD, drugs, CKD
40
What can cause hyperfibrinolysis?
F13 deficiency/dysfunction, PAI-1 deficiency, a2 antiplasmin deficiency
41
What causes acquired hemophilia A?
Sudden generation of autoantibodies against F8
42
What are some things that can predispose one to acquired hemophilia A?
CLL, adenocarcinomas, postpartum, autoimmune disorders, dermatologic disorders, drugs
43
Compare presentaiton of acquired vs hereditary hemophilia A
Acquired: Subcutaneous hematomas and muscle bleeding
Hereditary: joint bleeding
44
Describe mixing study of hemophilia A
Does not correct
45
What are 3 treatment strategies for acquired hemophilia A?
1. manage bleeding with agents that bypass F8
2. Remove autoantibody with immunosuppressive therapy
3. treat underlying cause
46
How do clotting factors differ in neonates?
vit K factors low, VWF and F8 high
47
In the pediatric bleeding questionnaire, what score indicates a bleeding disorder?
>2
48
How does vit K deficiency affect factor 5, factor 7, factor 8, TT, platelet count, fibrinogen, and D dimer?
Factor 5: no effect
Factor 7: decrease
Factor 8: no effect
TT: no effect
Platelet count: no effect
Fibrinogen: no effect
D dimer: no effect
49
How does liver disease affect factor 5, factor 7, factor 8, TT, platelet count, fibrinogen, and D dimer?
Factor 5: decrease
Factor 7: decrease
Factor 8: normal or increase
TT: increase
Platelet count: decrease
Fibrinogen: decrease
D dimer: normal
50
How does DIC affect factor 5, factor 7, factor 8, TT, platelet count, fibrinogen, and D dimer?
Factor 5: decrease
Factor 7: decrease
Factor 8: decrease
TT: increase
Platelet count: decrease
Fibrinogen: decrease
D dimer: increase
51
How does a congenital factor deficiency affect factor 5, factor 7, factor 8, TT, platelet count, fibrinogen, and D dimer?
Factor 5: decrease (depends)
Factor 7: decrease (depends)
Factor 8: decrease (depends)
TT: increase
Platelet count: no effect
Fibrinogen: decrease
D dimer: normal
52
What can be administered to stop mucosal bleeding in patients with hereditary hemophilia?
Tranexamic acid
53
Compare T1, T2, and T3 VWD
T1 and T3 are quantitative disorders: decreased VWD antigen (and proportionally decreased activity)
T2 is qualitative: decreased activity but normal antigen
54
How is VWD managed?
prevent bleeds, use DDAVP to increase F8 levels, tranexamic acid, cryoprecipitate
55
What are the 5 types of thrombocytopenia
ITP, HIT, and the TMAs: HUS, TTP and DIC
56
What causes ITP?
Immune-mediated destruction of platelets due to autoantibody production in BM - idiopathic of from lymphoma, leukemia, infections
57
How is ITP characterized?
Mucosal bleeds, purpura, history of autoimmune disorders
58
How is ITP diagnosed?
Diagnosis of exclusion: platelet count low but other blood markers ok.
59
How is ITP managed?
glucocorticoids as 1st line therapy to suppress immune system and then can do splenectomy if issue doesnt improve
60
When do you infuse platelets with thrombocytopenias?
Only with DIC! Dont transfuse platelets with HIT, TTP, HUS or ITP
61
What causes TTP?
primary or secondary- drugs, pregnancy, infection, stem cell transplant
62
How is TTP diagnosed?
Schistocytes on blood film and low ADAMTS-13 levels
63
What happens in TTP?
Low ADAPTS-13 levels means VWF multimers cant be cleaved so they accumulate and block blood flow
64
How is TTP treated?
plasma exchange to remove and replace VWF monomers
65
What is the pathophysiology of HUS?
Endothelial damage due to toxins (esp. Shiga toxin) or cancer, pregnancy, and autoimmune conditions causes acute kidney injury which leads to micro thrombosis
66
How is HUS diagnosed?
Acute kidney injury, schistocytes, and normal ADAMTS-13 levels
67
How is HUS managed?
Supportive: monitoring and IV fluids. Avoid antibiotics
68
What is the pathophysiology of DIC?
Overactivation of coagulation cascade that causes small clots
69
What can cause DIC?
Infection, cancers, trauma, obstetric issues
70
How is DIC diagnosed?
Schistocytes, elevated INR (Key!!), elevated D-dimer, low fibrinogen
71
How is DIC managed?
Supportive (IV fluids) and treat underlying condition
72
What is the pathophysiology of HIT?
Immune/antibody-mediated ADR to heparin resulting in platelet activation and thrombosis WITHOUT bleeding
73
How is HIT diagnosed?
Based on 4T score: thrombocytopenia, timing (acute/severe onset over 5-10d), thrombosis, and no other thrombotic causes
74
How is HIT managed?
stop all heparin and start alternative anticoagulant
75
What are risk factors for thrombosis?
Vichow's triad: stasis, injury, and hypercoagulability
76
what can cause hypercoagulability?
Cancer, certain drugs, hereditary or acquired hemostatic disorders
77
How is thrombosis prevented?
Early mobilization after surgery
78
What meds are given after surgery for low vs high thrombotic risk patients?
Low risk: 2500u dalteparin (LMWH) daily
High risk: 5000u dalteparin daily or heparin or a DOA
79
What does DVT diagnosis require? Describe
Objective test not just clinical assessment: do D-dimer test and if its positive then do a compression ultrasound
80
What is the clinical model for predicting DVT probability?
Wells rule: having active cancer, paralysis, stasis, tenderness, swelling, edema, Hx of thrombosis
81
What are some symptoms of PE?
pleuritic chest pain, dyspnea, syncope, tachycardia, hemoptysis
82
How is PE diagnosed?
With objective assessment: do V/Q scan and if theres a mismatch this is indicative of PE. Do a D-dimer test and if positive then do CT pulmonary angiogram
83
What are the 2 main goals of venous thromboembolism (VTE) treatment?
alleviation of symptoms and prevention of death due to PE
84
How is VTE treated?
Through anticoagluation: low mw heparin, warfarin, direct oral anticoagulants, etc.
85
What are contraindications for heparin or DOAs? what do you give instead?
renal failure
Give warfarin instead
86
What are contradictions for DOAs? What do you give instead?
Pregnancy and GI issues. Give LMWH instead
87
Compare treatment direction for VTE in cancer patients, those with major risk factors, and idiopathic men/women
Cancer: 6m
Risk factors: 3m
idiopathic men: indefinitley
idiopathic women: 6m
88
Are DVT and PE treated as outpatient or inpatient? Describe treatment of each
DVT: outpatient. Elevate limb, encourage activity, compression stockings, NSAID for pain
PE: inpatient. Activity as tolerated, NSAIDs, anticoagulants
89
What are 5 causes of hereditary thrombophilia?
1. Factor 5 Leiden
2. prothrombin gene mutation
3. Protein C deficiency
4. Protein S deficiency
5. Antithrombin deficiency
90
What can cause acquired thrombophilia?
Antiphospholipid Ab/lupus anticoagulant
91
What are 5 types of anticoagulants
1. unfractionated heparin
2. LMWH
3. Vitamin K agonists
4. Direct thrombin inhibitors
5. direct oral anticoagulants
