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30 Cards in this Set
- Front
- Back
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Four parts of hemostasis
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Vasoconstriction
Platelet plug formation (primary) Fibrin deposition (secondary hemostasis) Vessel repair and fibrinolysis |
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Steps of Primary Hemostasis, Requirements and things that can alter
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Impaired vessel constricts, platelets adhere to subendotheliam via VON WILLEBRAND factor (def causes excessive bleeding)
Platelets change shape, release granular contents (ADP, thromboxane, arachidonic acid) to attract more platelets. Aggregate and plug (platelet plug = primary hemostasis) Requires: Normal vessel, adequate platelet count (low is thrombocytopenia), normal platelet function (impaired by aspirin or NSAIDs), Von Willibrand factor. Fibrinogen to attach one platelet to another |
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Platelet granule contents
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Thromboxane
ADP Arachidonic Acid Attracts other platelets and helps lead to plug formation Thromboxane impaired by aspirin and NSAIDs |
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Secondary Hemostasis Steps, Requirements
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"Coagulation Cascade"
Tissue factor in subendothelium exposed to blood to start casacade by forming fibrin from fibrinogen (there connecting primary platelet plug) Tissue factor binds coag factors leading to thrombin activation and fibrin polymerization. NEED BOTH PLATELETS AND FIBRIN Thrombin is most essential enzyme, more thrombin = more fibrin |
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Liver Disease effect on bleeding
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Affects any cofactors made by liver
Fibrinogen primarily will be low and impairs both primary plug and secondary plug |
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Coagulation Cascade Overview
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Tissue factor binds Factor VIIa
VIIa activates Factors X and IX and then is quickly inhibited by Tissue factor pathway inhibitor (TFPI) Xa and Factor Va activate prothrombin to thrombin IXa and VIIIa activate more factor X. (IXa also activates itself) Thrombin activates Factor XIII and Fibrinogen (cleaves to fibrin monomers) XIIIa and fibrin monomers lead to cross-linked fibrin in a "stable clot" |
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Coagulation cascade propagation phase
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Activation of more Factor VIII, XI and V that ultimately lead to more factor Xa and thrombin
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Fibrinolytic System
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Thrombin promotes fibrin clot formation
Then Tissue Plasminogen Activator (tPA) and Urokinase (drug) can degrade clot Alpha 2 antiplasmin and Plasminogen activator Inhibitors normally keep clot from being broken down too early |
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Causes of DIC, test for
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cancer, gram negative sepsis, major trauma, pregnancy
Clots and fibrinolysis all over the body D-dimer test - marker for ongoing clot |
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Tests for Bleeding Disorders Primary vs Secondary and what alters
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Bleeding Disorders are more likely if there is bleeding in more places. Start with one test and work up do not order all at once
Primary CBC (platelet count and morphology) Platelet function (aggregation) (Dysfunction in asipirin or Vitamin E) VonWillibrand Factor (1% population, looks like thrombocytopenia) Secondary (fibrin formation), Clotting tests Prothrombin Time - Tests initiation phase of coag cascade. Factor VIIa and Tissue factor leading to Factor X activation and Prothrombin cleavage (Factors VII, X, V, II, I) Partial Thromboplastin Time - Evaluates Propagation phase, Factors IX, VIII, X, V, II, I to upregulate VIIIa and IXa to get more factor X and therefore more Thrombin Fibrinogen Thrombin Time - measures fibrinogen to fibrin |
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MCH and MCV on CBC
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MCH measures hemoglobin per cell and is low in anemia
MCV measures red cell volume and tells if it is macrocytic vs microcytic anemia (B12 def vs iron def) |
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Test monitored for Warfarin
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Prothrombin Time.
It affects more Initiation factors |
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Components of PT, PTT test and what low factors alter
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PT - patient plasma + thromboplastin + phospholipid +Ca and measure clot time.
Low VII, X, V, prothrombin, fibrinogen or warfarin lengthen PTT - Patient plasma + contact activator (silica, kaolin) + phospholipid + Ca and measure clot time Prolonged with low anything EXCEPT VII and XIII. Heparin prolongs Both collected in sodium citrate tubes. |
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What prolongs Fibrinogen and Thrombin Time tests
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Fibrinogen - decreased in liver failure, massive consumption (DIC)
Thrombin time - prolonged with low fibrinogen, heparin and direct thrombin inhibitor drugs |
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Considerations in bleeding eval
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Gender, Age, FHx, PMH (surgeries, trauma), Comorbid (chemo, liver, renal prob), exposure (rat poison), MEDs (NSAIDs, antibiotics), site and duration, previous episodes
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Type of Bleeding vs Etiology and subgroups for Primary Hemostasis
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Primary Hemostasis - Mucocutaneous manifestations or skin.
a) Vascular abnormalities - congenital (Hereditary hemorrhagic telangietasia, CT disorders) or acquired (aspirin, warfarin, heparin), collagen defects (Vit C), allergic purpura, senile purpura b) Platelet disorders - thrombocytopenia (impaired production, accelerated destruction, sequestration), platelet dysfunction (congenital, aspirin, clopidogril, acetaminophin, End stage renal disease c) Von Willibrand Disease - mostly low number but can have impaired quality |
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Causes of Thrombocytopenia
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Impaired production in bone marrow - acute leukemia or MDS, Alcohol, bone marrow fibrosis
Accelerated destruction - Immune thrombocytopenia (ITP) due to Ab's (SLE, RA, IBD) or non immune consumption (DIC), malignant HTN Sequestration - Splenic infiltration/enlargement (leukemia, lymphoma) Liver cirrhosis |
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Suspicion of Hereditary Hemorrhagic Telangiectasia
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Mucocutaneous and skin bleeds
Due to vascular abnormality Epitaxis and intracranial bleeds |
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Bernard-Soulier Disease, test
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Defect in von Willibrand factor receptor (glycoprotein 1b) leading to Platelet dysfunction
Thrombocytopenia and giant platelets Can be fatal |
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Glanzmann's thrombasthenia, test
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Defect in fibrinogen receptor (glycoprotein 2b3a) leading to platelet dysfunction
NORMAL Platelet count and morphology |
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Primary causes of Hematemesis, Melana, Menorrhagia, Hematuria, Hematoma, Hemoptysis
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MOST pts with bleeding do not have coag disorder but due to other disease (still check if suspect)
a) Hematemesis - portal HTN/cirrhosis b) Melena - aspirin induced gastritis, colon cancer c) Menorrhagia - hormone imbalance d) Hematuria - renal stone e) Hematoma - trauma f) Hemoptysis - pneumonia |
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Drugs leading to platelet dysfunction
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Aspirin, acetaminophen, clopidogrel, antibiotics
Heparin and warfarin can impair vascular system and also lead to bleeding Non-aspirin anti-inflammatory drugs with reversible antiplatelet inhibition is preferrable No aspirin a week before invasive procedure |
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ESRD cause of platelet dysfunction
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Causes uremia which somehow leads to lower multimers of vWF and an impaired fibrinolytic system
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Type of Bleeding vs Etiology and subgroups for Secondary Hemostasis and fibrinolytic system
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Bleeding for Soft tissue/joints. Hemoarthrosis or large hematoma
Coagulation factor deficiencies usually Fibrinolytic system - DELAYED bleeding due to too much fibrinolysis |
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Hemophilia A vs B, sites of bleeding, most severe, testing, treatment
Severe, moderate and mild |
X-linked so males>>>females
A - Factor VIII deficiency (80% cases) B - FActor IX deficiency Clinically look same, MAY have neg FHx (1/3 new mutation) Women carriers may have lower levels and have problems with surgery Sites: Hemarthroses (80%) (ankles, hip, knees, elbows), Hematomas (pharyngeal in airway, abdominal, intramuscular [nerve compression risk]) Most serious: CNS (spontaneous, traumatic, intracerebral, intraspinal) Testing: PT and PTT test. Norm PT and PTT should be prolonged. Then get Factor VIII level and Factor IX level tests. Treat: concentrated Factor Severe - <1%, spontaneous bleeding (% expected value) Moderate - 1-5%, bleeding post minor trauma or surgery Mild - 6-30%, increased bleeding post major surgery or trauma |
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Acquired and Congenital disorders suspected with following
a) Long PT and Normal PTT b) Normal PT and Long PTT c) Long PT and Long PTT d) Normal PT and PT |
a) Acquired Vit K def, early liver failure, early DIC; Congenital Factor VII def
b) Aquired heparin, Factor VIII inh.; congenital Factors VIII, IX, or XI def or severe vWD c) Acquired DIC, liver disease, amyloidosis (factor X def); congenital fibrinogen, prothrombin, Factor V or X def d) Acquired thrombocytopenia, qualitative platelet disorder, scurvy; congenital mild factor def, mild vWD, factor XIII def PT and PTT don't depend o nvWF |
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Non hemophilia causes of secondary hemostasis disorder
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Congenital def in Fibrinogen, Factors II, V, VII, X, XI and XIII
Acquired liver disease, anticoagulationa gents (warfarin, heparin) |
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Hemostatic Defects in Liver Disease and possible mechanisms
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Impaired coagulation - less synthesis of clotting factors, Vit K def
Thrombocytopenia and platelet function defects - Splenomegaly, failure to clear platelet inhibitors, decreased membrane receptors due to hyperfibrinolysis DIC - procoagulants from liver cells, endotoxins not removed, failure to clear activated clotting factors, LOW PROTEIN C AND S Systemic Fibrinolysis - Reduced alpha2 antiplasmin, don't clear fibrinolytic enzymes. Release of TPA in surgery |
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Indications for anticoagulants, Agents and MOA
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Prophylaxis and to treat VENOUS THROMBOSIS and thromboembolic complications of Afib or mechanical heart valves
Warfarin - oral - prevents liver synthesis of Vit K coagulation factors (II, VII, IX and X) Heparin - subQ or IV - blocks cascade at Factors Xa and thrombin Direct thrombin inhibitors Dabigatran (Pradaxa), Argatroban, bivalirudin |
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Treating vWD
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Desmopressin - releases endothelial stores of vWF
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