Section 11: Fibrinolytic and Thrombotic Flashcards
plasmin functions
- lyses fibrin and fibrinogen
- inactivates factors Va and VIIIa
- degrades factor XIIa
primary fibrinolysis (fibrinogenolysis)
- always pathological
- overactivation of plasmin and/or
- overwhelms plasmin inhibitors
- other physiological causes
secondary fibrinolysis (fibrinolysis)
- normal and pathological
- pathological if overactivation of plasmin and/or overwhelms plasmin inhibitors
overactivation of plasmin in liver disease and exogenous activators
- 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
stuff indicated in causing thrombosis
- 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
anti-thrombin deficiency
- thrombosis
- often family history of pathological thrombi and emboli
Protein C and Protein S deficiencies
- thrombosis
- can’t inactivate Va or VIIIa
- can’t liberate tPA (fibrinolytic)
Protein Z and ZPI deficiencies
- thrombosis
- can’t degrade Xa
- ZPI can’t degrade XIa
heparin cofactor II deficiency
- thrombosis
- decreased neutralization of thrombin
activated protein C resistance (APC-R)
- aka Factor V Leiden
- mutation of Factor V gene
- Factor V resistant to lysis or inactivation by APC
- 20% new thrombosis
expected APC-R PT and APTT results?
Normal for both because Va is functioning
APC-R clot based assay procedure
- Add APTT reagent + FV-depleted plasma + pt plasma
- Split into two aliquots
- Add CaCl2 to one aliquot
- Add CaCl2 + APC to the second aliquot
APC-R clot based assay principle
If APC-resistant, then adding APC will prolong clot time LESS than the non-resistant sample
XIIa function
convert plasminogen to plasmin
XII deficiency causes
thrombosis
factor XI deficiency (hemophilia C)
bleeding
not thrombosis
dysfibrinogenemia
- 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
prekallekrein and HMWK deficiencies
- typically asymptomatic
- may see thrombosis due to lack of activation of plasminogen to plasmin
- PT normal and APTT prolonged
plasminogen deficiency
- thrombosis
- type 1: decrease in activity and protein (deficiency)
- type 2: dysfunctional
tPA deficiency
- thrombosis
- results in decreased activation of plasminogen to plasmin
prothrombin mutation
- prothrombin G20210A
- single point mutation in prothrombin gene
- causes increased prothrombin levels -> thrombosis
increased homocysteine
- defect in homocysteine metabolism
- increased homocysteine levels -> thrombosis
- mechanism unknown
ebola association with thrombocytopenia
may be associated with bone marrow suppression but it’s often not enough to account for bleeding on its own
list possible causes of bleeding in ebola
- thrombocytopenia
- platelet dysfunction
- DIC
- hepatic coagulopathy
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
explain possible hepatic coagulopathy cause of ebola
associated with viral-induced necrosis
COVID-19 early CBC results
looks fairly normal
what happens as COVID-19 progresses?
lymphopenia
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
presence of what cell type during COVID-19 may represent a better outcome?
reactive lymphs
suggests virus-specific T-cell production
hypercoagulopathy of COVID-19 infection
- endothelial cell injury especially lungs
- stasis: immobilization slows blood flow
- hypercoagulable state
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
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
T/F
Severe hypoxia stimulates thrombosis in COVID-19 infection
True
COVID-19 hypercoagulable state molecular events
- neutrophil extracellular traps can worsen inflammation and thrombosis if not regulated
- bradykinins in inflammation
- hyperviscosity slows blood flow
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
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
treatment of thromboinflammation
- heparin antithrombotic
- prophylactic LMWH
