Ch. 4 part. 2 Flashcards
Coagulation cascade
amplifying enzyme conversions culminating in thrombin formation
Thrombin
most important coagulation factor. converts fibrinogen to fibrin (fibrin gel). Proinflammatory.
2 standard coagulation pathway assays
Prothrombin time (PT) and Partial Thromboplastin time (PTT)
Prothrombin time (PT) assay
Extrinsic pathway protein function. Factors 2, 5, 7, 10, and fibrinogen.
PT assay accomplished how?
adding tissue factor and phospholipids to citrated plasma (want to prevent spontaneous clotting). adding exogenous calcium.
Partial Thromboplastin time (PTT) assay
Intrinsic pathway protein function. Factors 2, 5, 8-12, and fibrinogen.
How is PTT assay initiated?
By addition of negatively charged particles (activate factor 12, hagemans)
Protease Activated Receptors (PARs)
mechanism of thrombin effects.
3 categories of endogenous anticoagulants
antithrombins (antithrombin III), Protein C and S, TFPI
Antithrombin (antithrombin III)
inhibit thrombin and factors 9-12a. Activated by binding heparin-like molecules.
Protein C and S
Vitamin K-dependent. inhibit factors 5a and 8a.
TFPI
produced by endothelium. inhibits tissue factor 7a.
3 primary abnormalities that lead to thrombosis (Virchow’s triangle)
Endothelial injury, turbulence/stasis, hypercoagulability
Endothelial cell injury
Cardiac chambers (after MI), ulcerated plaques, vasculitis
Insults of endothelial injury
Hypertension, turbulence, bacterial endotoxin, radiation, metabolic abnormalities, toxicity smoke
Turbulence
countercurrents or pockets of stasis.
stasis and turbulence promote
pro-coagulation by bringing platelets in contact to epithelium.
Hypercoagulability
thrombophilia. any alteration of coagulation that predisposes thrombosis.
Primary hypercoagulability (genetic) gene locations
Point mutations at Factor 5 and prothrombin genes.
primary hypercoag cause
elevated levels of homocysteine. (thioester linkages- thrombic), deficiency of antithrombin III, protein C or S.
Clinical presentation of primary hypercoag
venous thrombosis, recurrent thromboembolism
Heparin-induced thrombocytopenia (HIT) syndrome occurs when?
following the administration of unfractionated herparin, which induces Ab production to recognize complexes of heparin and platelet factor 4 (and like molecules)
Effects of HIT syndrome
causes platelet activation, aggregation, and consumption leading to thrombocytopenia (hence the name)
Antiphospholipid antibody syndrome (or lupus anticoagulant syndrome) clinical manifestations
recurrent thrombosis, miscarriages, cardiac valve vegetations, thrombocytopenia, pulmonary hypertension, pulmonary embolism, etc.. has primary and secondary forms.
Antiphospholipid antibody syndrome (lupus anticoagulant syndrome) effect.
antibodies induce a hypercoagulable state. endothelial injury results, activation of platelets and complements
Secondary antiphospholipid antibody syndrome
individuals who have a well defined autoimmune disease (SLE) and exhibit hypercoagulability
Primary antiphospholipid antibody syndrome
exhibit only the manifestations of the hypercoagulable state. do not have autoimmune disease
Arteriole thrombi
usually due to turbulence or endothelial injury. Grow retrograde.
Venous thrombi
usually due to stasis. grow with blood flow.
Lines of Zahn (antemortem clot)
pale platelet and fibrin deposits alternating with darker red cell-rich layers. distinguishes between antemortem and postmortem
Postmortem clot
RBC settle to bottom and have plate platelets and fibrin on top layer. (chicken fat top)
Mural thrombi
thrombi occurring in the heart chambers or aortic lumen
promotions of mural thrombi
abnormal myocardial contraction (arrhythmias, MI), endomyocardial injury (myocarditis, catheter)
Aortic thrombi
in the aorta, usually due to aneurysm.
Arterial thrombi
frequently occlusive. common sites: coronary, cerebral and femoral arteries
Venous thrombi (phlebothrombosis)
long cast of the lumen, formed by stasis. usually in LE
vegetations
thrombi on heart valves. caused by blood-borne bacteria or fungi. (infective endocarditis)
sterile vegetations
nonbacterial thrombotic endocarditis.
Libman-Sacks endocarditis
sterile verrucous endocarditis. (SLE)
DVT
Larger leg veins. may cause pulmonary infarcts. collateral channels offset.
Disseminated intravascular coagulation (DIC)
sudden or insidious systemic thrombi. cause organ dysfunction in brain, heart, lungs, kidneys.
DIC complication
uses all platelets and coagulation factors and causes bleeding catastrophe
what is an embolus
detached intravascular solid, liquid, or gaseous mass
Pulmonary embolism (large emboli)
95% originate from LE. large emboli - sudden death (right heart failure- cor pulmonale). saddle emboli.
Pulmonary embolism (small)
minimal Sx, except inadequate bronchial circulation. causes: immobile, HF, hypercoagulable
Pulmonary embolism clinical course
cardiopulm resus. ECG has rhythm but do not palpate pulse. survival mimics MI
Pulmonary embolism Dx
spiral CT. may indicate with Hampton Hump, lower right lung
Pulmonary embolism gross exam
75% lower lung, wedge shaped, hemorrhagic, fibrinous exudate,
Pulmonary embolism microscopic exam
ischemic (coagulative) necrosis, infected embolus (neutrophil inflamm, septic infarct)
Fat and marrow embolism
fat globules, hematopoietic marrow. Fractured long bones, soft tissue trauma and burns.
Air embolism
gas bubbles in circulation. need more than 100cc air.
Air embolism effect
obstruct vascular flow (distal ischemic injury)
Air embolism cause
decompression sickness. (decrease in atm pressure)
The bends
gas bubbles in skeletal muscle and joints
the chokes
gas bubbles in vasculature. causes: edema, hemorrhage, focal atelectasis or emphysema. (pulm distress)
Caisson disease
chronic decompression sickness. (femoral heads, tibia, humeri)
Amniotic fluid embolism
complication of labor. dyspnea, cyanosis, shock, neurologic impairment
Cause of amniotic fluid embolism
infusion of amniotic fluid or fetal tissue into maternal circulation via tear in placenta.
Shock causes
hemorrhage, trauma or burns, MI, pulmonary embolisms, microbial sepsis
consequences and 3 categories of shock
impaired tissue perfusion and hypoxia. cardiogenic, hypovolemic, septic shock.
hypovolemic and cardiogenic shock
hypotension, weak rapid pulse, cyanosis
septic shock
flushing due to peripheral vasodilation
