Section 11: Fibrinolytic and Thrombotic Flashcards
1
Q
plasmin functions
A
- lyses fibrin and fibrinogen
- inactivates factors Va and VIIIa
- degrades factor XIIa
2
Q
primary fibrinolysis (fibrinogenolysis)
A
- always pathological
- overactivation of plasmin and/or
- overwhelms plasmin inhibitors
- other physiological causes
3
Q
secondary fibrinolysis (fibrinolysis)
A
- normal and pathological
- pathological if overactivation of plasmin and/or overwhelms plasmin inhibitors
4
Q
overactivation of plasmin in liver disease and exogenous activators
A
- liver disease: decreased inhibitors of fibrinolytic system thereby increasing fibrinolysis, decreased alpha2-antiplasmin
- plasmin free to attack not only fibrin, but also fibrinogen, factors V and VIII -> bleeding - exogenous activators: streptokinase, urokinase, tPA
- Euglobulin test
5
Q
stuff indicated in causing thrombosis
A
- major tissue trauma and surgery
- obesity
- complications of pregnancy (immobility, dead fetus syndrome, amniotic fluid embolus, HELLP, increase in factors VII, VIII, IX, XII, and I…etc)
- oral contraceptives
6
Q
anti-thrombin deficiency
A
- thrombosis
- often family history of pathological thrombi and emboli
7
Q
Protein C and Protein S deficiencies
A
- thrombosis
- can’t inactivate Va or VIIIa
- can’t liberate tPA (fibrinolytic)
8
Q
Protein Z and ZPI deficiencies
A
- thrombosis
- can’t degrade Xa
- ZPI can’t degrade XIa
9
Q
heparin cofactor II deficiency
A
- thrombosis
- decreased neutralization of thrombin
10
Q
activated protein C resistance (APC-R)
A
- aka Factor V Leiden
- mutation of Factor V gene
- Factor V resistant to lysis or inactivation by APC
- 20% new thrombosis
11
Q
expected APC-R PT and APTT results?
A
Normal for both because Va is functioning
12
Q
APC-R clot based assay procedure
A
- Add APTT reagent + FV-depleted plasma + pt plasma
- Split into two aliquots
- Add CaCl2 to one aliquot
- Add CaCl2 + APC to the second aliquot
13
Q
APC-R clot based assay principle
A
If APC-resistant, then adding APC will prolong clot time LESS than the non-resistant sample
14
Q
XIIa function
A
convert plasminogen to plasmin
15
Q
XII deficiency causes
A
thrombosis
16
Q
factor XI deficiency (hemophilia C)
A
bleeding
not thrombosis
17
Q
dysfibrinogenemia
A
- most asymptomatic
- may be resistant to fibrinogenolysis and/or once clot is formed it is resistant to fibrinogenolysis -> thrombosis
- can also be present as a bleeding disorder or both bleeding + thrombosis
18
Q
prekallekrein and HMWK deficiencies
A
- typically asymptomatic
- may see thrombosis due to lack of activation of plasminogen to plasmin
- PT normal and APTT prolonged
18
Q
plasminogen deficiency
A
- thrombosis
- type 1: decrease in activity and protein (deficiency)
- type 2: dysfunctional
19
Q
tPA deficiency
A
- thrombosis
- results in decreased activation of plasminogen to plasmin
20
Q
prothrombin mutation
A
- prothrombin G20210A
- single point mutation in prothrombin gene
- causes increased prothrombin levels -> thrombosis
21
Q
increased homocysteine
A
- defect in homocysteine metabolism
- increased homocysteine levels -> thrombosis
- mechanism unknown
22
Q
ebola association with thrombocytopenia
A
may be associated with bone marrow suppression but it’s often not enough to account for bleeding on its own
23
Q
list possible causes of bleeding in ebola
A
- thrombocytopenia
- platelet dysfunction
- DIC
- hepatic coagulopathy
24
explain possible DIC cause of ebola
- TF3 released from infected monos/macrophages
- cytokine storm
- inflammation -> vascular lesions
- plt activation and unusually large vWF resulting in a TTP-like syndrome
- fibrin deposited in organs
25
explain possible hepatic coagulopathy cause of ebola
associated with viral-induced necrosis
26
COVID-19 early CBC results
looks fairly normal
27
what happens as COVID-19 progresses?
lymphopenia
28
possible causes of lymphopenia in COVID-19 infection
- virus infects and kills lymphs
- virus destroys lymphatic organs
- disordered inflammatory cytokines -> lymph apoptosis
- inhibition of lymphs by metabolic molecules such as lactic acid that suppress lymph proliferation
29
presence of what cell type during COVID-19 may represent a better outcome?
reactive lymphs
suggests virus-specific T-cell production
30
hypercoagulopathy of COVID-19 infection
- endothelial cell injury especially lungs
- stasis: immobilization slows blood flow
- hypercoagulable state
31
explain endothelial cell injury in COVID-19 coagulopathy
- direct invasion of ECs
- cytokine storm -> systemic inflammatory response
- TNF-alpha and IL-6 released, TNF-alpha strong inducer of TF3 -> plt activation and coagulation
32
lab results of COVID-19 associated coagulopathy (CAC)
- high D-dimer levels (poor prognosis)
- elevated VIII:C and fibrinogen
- vWF antigen increased due to injury to endothelium and reduced ADAMTS13 activity (large multimers)
- excess thrombin formation and early fibrinolysis shutdown -> higher TFPI
- decreased AT and protein C
- possible antiphospholipid antibodies
33
**T/F**
Severe hypoxia stimulates thrombosis in COVID-19 infection
True
34
COVID-19 hypercoagulable state molecular events
- neutrophil extracellular traps can worsen inflammation and thrombosis if not regulated
- bradykinins in inflammation
- hyperviscosity slows blood flow
35
coagulation test results for COVID-19 infection
- PT and APTT normal or sl prolonged
- plt count normal or increased
- fibrinogen increased
- D-dimer increased (associated with ICU and respirator)
- should monitor for renal impairment
36
how to distinguish COVID-19 from DIC even tho both have increased D-dimer?
- **COVID**: thrombosis, high fibrinogen, high factor VIII
- **acute DIC**: bleeding, low fibrinogen, low factor VIII
37
treatment of thromboinflammation
- heparin antithrombotic
- prophylactic LMWH
