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What disorder:
Genetic deficiency
Associated with DVT and pulmonary embolism
Serine proteases not inhibited
Negative feedback to cascade impaired
Lab test used: Antithrombin activity assay
Antithrombin (AT) deficiency
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What disorder:
Vitamin K-dependent regulatory proteins that inactivate factors V and VIII
Can cause superficial and deep vein thrombosis (DVT) and/or pulmonary embolism
Protein C or Protein S deficiencies
-
What disorder:
Associated with thrombosis
Prolonged PTT
Factor XII assay confirms
Faxtor XII (Hageman or Contact factor) deficiency
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What disorder:
Associated with thrombosis
Prolong PTT
PTT shortens in patient plasma incubated with kaolin
Prekallikrein (Fletcher factor) deficiency
-
What disorder:
Associated with thrombosis
Slightly prolonged PTT
HMWK (Fitzgerald factor) deficiency
-
What disorder:
Associated with thrombosis
Inability to generate plasmin
Plasminogen deficiency
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What disorder:
Cause of thrombosis because of an amino acid substitution
Causes thrombin generation and subsequent fibrin clot formation
Lab test used: PCR-based molecular assay to single point mutation in the gene for factor V
Most common hereditary cause of thrombosis
Factor V Leiden (Activated Protein C Resistance - APCR)
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What disorder:
Cause of thrombosis because of an amino acid substitution
May have slightly elevated prothrombin level
Lab test used: PCR-based molecular assay
2nd most common hereditary cause of thrombosis
Prothrombin gene mutation 20210
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What disorder:
Abnormal structure of fibrinogen
Caused by gene mutations
Associated with either bleeding or thrombosis
Dependent on the specific gene mutation
Dysfibrinogenemia
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What is the most common hereditary bleeding disorder?
von Willebrand disease
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What disorder:
Abnormalities in both primary and secondary hemostasis
Caused by a defect that is needed for platelet adhesion to collagen in primary hemostasis
The defect is also a carrier protein for factor VIII:C in secondary hemostasis
Mild-Moderate bleeding
Decreased vWF:RCo, vWF:Ag, and VIII:C
Abnormal platelet aggregation with ristocetin
Variable PTT
Prolonged bleeding time
von Willebrand disease
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How is von Willebrand treated?
- Factor VIII concentrates
- DDAVP (deamino-D-arginine-vasopressin) - used to raise plasma levels of vWF and VIII:C
- Cryoprecipitate
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What disorder:
Sex linked disorder transmitted on the X chromosome by carrier women to their sons
Bleeding symptoms are proportional to the degree of the factor deficiency
Spontaneous bleeding occurs often and is especially bad in joint regions
Prolonged PTT
Factor VIII:C assay to confirm
- Factor VIII:C deficiency
- (hemophilia A or classic hemophilia)
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How is Factor VIII:C deficiency (hemophilia A, classic hemophilia) treated?
- Cryoprecipitate and factor VIII concentrates are used
- In mild cases, DDAVP can be used to stimulate the release of VIII:C and vWF from stored reserves
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What disorder:
Sex linked recessive
Bleeding symptoms are proportional to degree of deficiency
Prolonged PTT
Factor IX assay to confirm
- Factor IX (Christmas factor) deficiency
- (hemophilia B or Christmas disease)
-
How is Factor IX (hemophilia B, Christmas disease) treated?
FFP or Factor IX concentrates
-
What disorder:
Mainly seen in the Ashkenazi Jewish population
Characterized by clinical bleeding that is asymptomatic until surgery or trauma
Prolonged PTT
Factor XI assay to confirm
- Factor XI deficiency
- (hemophilia C)
-
What disorder:
Spontaneous bleeding of mucosa, intestines, and intracranial sites
Prolonged bleeding time
Decreased fibrinogen concentration
Prolonged PT, PTT, and thrombin time
- Factor I deficiency
- (fibrinogen)
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What disorder:
Spontaneous bleeding
Delayed wound healing
Unusualy scar formation
Increased incidence of spontaneous abortion
Abnormal 5.0 M Urea test
Enzymatic and immunologic studies can be done
- Factor XIII deficiency
- (fibrin/clot-stabilizing factor)
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What disorder:
Results in decreased synthesis of coag or regulatory proteins
Causes impaired clearance of activated hemostatic components
Prolonged PT, PTT, bleeding time
Decreased plt counts
Hepatic disease
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Where is Vitamin K synthesized?
Produced by normal intestinal flora
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What is Vitamin K needed for?
Liver synthesis of functional factors II, VII, IX, and X
-
How can vitamin K deficiency occur?
- Oral antibiotics
- Warfarin/coumadin
- Decreased absorption resulting from obstructive jaundice
- Breast fed babies because breast milk is sterile
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What disorder:
Predisposing condition triggers systemic clotting
Leads to systemic fibrinolysis and bleeding
Prolonged PT, PTT, thrombin time
Decreased Plt count, antithrombin, fibrinogen
Fibrin and FDPs are present
Systemic thrombotic event causes multiple organ failure and systemic lysis ultimately leads to severe hemorrhage
DIC with secondary fibrinolysis
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What disorder:
Plamsminogen is inappropriately activated to plasmin in the absence of clot formation
Plasmin circulates free in plasma and destroys factors I, V, VIII
Prolonged PT, PTT, thrombin time
Decreased fibrinogen
Fibrinogen degradation products are present BUT fibrin degradation products are absent b/c no clot formation
Hemorrhagic symptoms may resemble DIC
Primary fibrinogenolysis
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What would happen if you collect coag tests in a glass tube?
Plain glass tubes will activate the intrinsic pathway, including the activation of the contact factors (prekallikrein, XI, XII)
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What is the ratio of blood to anticoagulant in sodium citrate tubes?
9:1
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What is the specimen processing time limit for PT and PTT?
- PT: 24 hours room temp
- PTT: 4 hours room temp
-
What is the best temperature to test for coagulation tests?
37 degrees celcius
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What factors does the PTT test screen for?
- XII (Hageman Factor or Contact Factor)
- XI
- Prekallikrein
- HMWK
- IX (Christmas Factor)
- VIII (Anti-hemophilic Factor)
- X (Stewart Prower)
- V (Labile Factor)
- II (Prothrombin)
- I (Fibrinogen)
- (Intrinsic and common pathways)
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What test screens for:
XII (Hageman or Contact Factor)
XI
Prekallikrein
HMWK
IX (Christmas Factor)
VIII (Anti-hemophiliac Factor)
X (Stewart Prower Factor)
V (Labile Factor)
II (Prothrombin)
I (Fibrinogen)
PTT
-
What 2 reagents are needed to test for PTT?
- Platelet phopholipid substitute with an activator (kaolin, celite, silica, or ellagic acid)
- Calcium chloride
-
What is the normal reference range for PTT?
23-35 seconds
-
What clinical conditions are associated with a prolonged PTT?
- Factor deficiencies in the intrinsic/common pathways
- Acquired circulating inhibitor (heparin, lupus, or antibody to a specific factor)
-
What factors does the PT test screen for?
- VII (Stabile Factor)
- X (Stewart Prower Factor)
- V (Labile Factor)
- II (Prothrombin)
- I (Fibrinogen)
- (extrinsic and common pathway)
-
What test screens for:
VII (Stabile Factor)
X (Stewart Prower Factor)
V (Labile Factor)
II (Prothrombin)
I (Fibrinogen)
PT
-
What reagents are used to test for PT?
- Thromboplastin source (tissue factor)
- Calcium chloride
-
What is the normal reference range of PT?
10-14 seconds
-
What is used as a means of standardizing PT reporting worldwide - it is not dependent upon thromboplastin reagent or instruments?
INR
-
What is the calculation for INR?
 - ISI: is the international sensitivity index for the thromboplastin reagent, which is provided by the manufacturer (lot number and instrument specific)
-
What can a prolonged PT indicate?
Factor deficiencies in the extrinsic/common pathways
-
What test will differentiate a factor deficiency from a circulatory inhibitor?
Mixing study
-
What does a shortening of the time in a mixing study indicate?
- Factor deficiency
- (hereditary, acquired, or liver disease)
-
What does a partial or no correction with a mixing study indicate?
- Circulating inhibitor
- (heparin, lupus inhibitor, VIII inhibitor, IX inhibitor)
-
What test is used for fibrinogen?
- Fibrinogen level
- Thrombin time
-
What test is used to confirm a suspected factor deficiency?
Factor assays
-
What test differentiates an unstable clot that forms in factor XIII deficiency and a factor XIIIa stabilized clot and what are the results?
- 5.0 M urea clot solubility test
- XIII: dissolves in 5.0 M urea
- XIIIa: remains intact in 5.0 M urea
-
What test is used to see if the lupus inhibitor is present or not and what is the result?
- Dilute Russell viper venom
- If lupus inhibitor is present, the venom is neutralized, and the test is prolonged
-
What test:
Usually a point of care test performed at a clinic, cardiac cath lab, or surgical suite
Most often used to monitor high dose heparin therapy during coronary artery bypass surgery
Activated clotting time (ACT)
-
What test is used to see if either fibrin degradation products or fibrinogen degradation products are present?
- FDPs
- (fibrin degradation products)
-
What test is highly specific for fibrin degradation products only?
D-Dimer Assay
-
How does Heparin therapy work and what must be monitored?
- Antithrombin/heparin complex inhibits serine proteases (XIIa, XIa, IXa, Xa, IIa, and kallikrein) - which is immediate
- Monitor PTT (supposed to be 1.5-2 times a patient's baseline PTT) and platelet counts (for heparin induced thrombocytopenia)
-
Can heparin therapy be reversed?
-
How does Warfarin (Coumadin) therapy work?
- Vitamin K antagonist
- Inhibits liver synthesis of functional prothrombin group factors II, VII, IX, X
-
Can Warfarin (Coumadin) be reversed?
- Yes
- Vitamin K can be administered
-
What needs to be monitored when giving Warfarin (Coumadin) therapy?
- PT
- INR
- (INR therapeutic range for most conditions is 2-3)
-
What medication is used in hemostasis:
Lower risk of heparin induced thrombocytopenia
Mainly an anti-Xa inhibitor, anti-IIa response is reduced
Low-molecular weight heparin
-
What medication is used in hemostasis:
Inactivates thrombin only
Does not require antithrombin to work
Used in place of unfractionated or low molecular weight heparin when HIT is suspected
Prolongs PT, PTT, and thrombin time
Direct thrombin inhibitor
-
What medication is used in hemostasis:
Can be used to lyse existing clots
Reestablish vascular perfusion
Convert plasminogen to plasmin - which destroys the fibrin clot, factors I, V, VIII
Affected tests: PT, PTT, thrombin time, fibrinogen, FDP, and D-Dimer
Fibrinolytic therapy
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What medication is used in conjunction with other anticoagulant therapies to prevent recurrence of thrombotic events?
- Antiplatelet medications
- (aspirin, Plavix, ticlopidine, and nonsteroidal anti-inflammatory drugs/NSAIDS)
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