Med Tech-Advanced Coagulation
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What is the anticoagulant of choice?
How does sodium citrate prevent clotting?
By binding calcium ions, which are needed for most steps in coagulation.
How are photo-optical detection systems used in clot detection?
Increase in turbidity as a soluble fibrin is converted to insoluble fibrin seen as a change in optical density
What does prothrombin time test?
The extrinsic pathway VII, X, V, II, and I.
What reagent is used to test prothrombin time and what does it contain?
Thromboplastin (Innovin) contains a source of tissue factor, phospholipid and calcium ions
What does Activated Partial Thromboplastin Time (APTT) test?
The intrinsic pathway XII, XI, IX, VIII, X, V, II, and I.
What reagent is used to test APTT and what does it contain?
Activator (particulate or chemical), phospholipid and Calcium chloride.
What is performed if an APTT screening test is abnormal?
A mixing study using equal amounts of patient plasma and pooled normal plasma. If there is a deficiency, mixture will correct; no correction indicates the presence of an interfering substance.
What is performed if there is a factor deficiency observed?
Factor Assay which will identify the level of one specific factor; always uses a specific factor deficient plasma.
What is thrombin time?
A qualitative measure of fibrinogen; sees how long it takes to clot fibrinogen in patient's plasma using an outside source of thrombin; should happen within normal reference range.
What reasons may cause the thrombin time to be prolonged?
- 1. decreased amount of fibrinogen
- 2. heparin is present (interferes with thrombin's ability to convert fibrinogen to fibrin)
- 3. increased fibrin split products (interfere with thrombin)
What is a factor XIII screen?
A test where thrombin activates Factor XIII, which then converts hydrogen bonds between fibrin polymers to covalent bonds, making insoluble cross-linked fibrin polymers.
What happens if Factor XIII is decreased or absent?
Fibrin polymers become soluble in 5M urea or 1% monochloroacetic acid.
What are two types of bleeding that occur?
Platelet type and coagulation factor bleeding
When is a mixing study performed?
If PT and APTT screening is abnormal. A mixing study will correct the range toward normal.
How is a mixing study interpreted when no correction can be achieved?
No correction indicates the presence of an interfering substance.
When a deficiency is identified, what test is run?
A factor assay. A factor assay identifies a specific factor by using known plasma that is deficient for the plasma factor that you are screening for. Another assay is run along side it with a known amount of the factor, and the values are compared.
What is prothrombin time?
A qualitative measure of fibrinogen. This test allows us to see how long it takes to clot fibrinogen in a patient's plasma using an outside source of thrombin.
What would possible reasons be for a prolonged thrombin time?
- 1. There is a decreased amount of fibrinogen
- 2. There is an increase in split fibrin products (interfere with thrombin)
What is the factor XIII screen test and when is it used?
If fibrin XIII is decreased or absent, fibrin polmers are soluble in 5M urea or 1% monochloroacetic acid. Remember, thrombin activates Factor XIII, converting hydrogen bonds between fibrin polymers to covalent bonds, making INSOLUBLE CROSS-LINKED FIBRIN POLYMERS
What is the relationship between thrombin and Factor XIII?
Thrombin activates Factor XIII, converting hydrogen bonds between fibrin polymers to covalent bonds, making INSOLUBLE CROSS-LINKED FIBRIN POLYMERS
Name two types of bleeding?
Platelet Type and Coagulation Factor.
What is the source and symptoms of Platelet Type bleeding?
Mucocutaneous where the skin and mucous membrane are affected with signs and symptoms consisting of petechiae, purpura, ecchymoses, nose and gum bleeds, menstrual, GI and GU bleeding.
What is the source and/or symptoms of Platelet Type bleeding?
- Joint - hemarthroses
- Deep Muscle - hematoma
What are some coagulation factor defects?
- 1. Decreased synthesis of factors
- 2. synthesis of abnormal (non-functional) molecule
- 3. loss or consumption
What is the difference between a single factor deficiency and multiple factor deficiencies?
Single factor is genetic and multiple factor are acquired (Vit. K deficiency, liver disease, DIC, dilution, renal disease)
What tests are used to screen for possible bleeding disorders?
- 1. CBC: including platelets
- 2. Closure time (platelet function)
- 3. PT
- 4. APTT
- 5. Mixing studies
What is the most common inherited, single factor deficiency? What is the inheritance pattern? What Factor?
- Hemophilia A, sex-linked recessive,
- Factor VIII
What is the treatment for factor replacement during incidences such as deep muscle bleeding?
DDVAP - desmopressin antidiuretic hormone. Often used in cases of Hemophilia A.
How does DDVAP work?
It stimulates the release of vWF from endothelial cells and increases water re-adsorption by binding to V2 receptors in the renal collecting ducts.
What population and situation would you see factor VIII inhibitors in non-hemophiliacs?
- 1. elderly
- 2. pregnant or post-partum
- 3. immunologic disorders
What hereditary deficiency is known as the Christmas Disease? What is the inheritance pattern? What Factor?
Hemophilia B, sex-linked recessive, Factor IX.
What is the treatment of Hemophilia B and how may it be acquired if not inherited?
Treated with Factor IX concentrates and acquired through liver disease, Vitamin K deficiency, and renal disease inhibitors.
What factor deficiency has a high incidence in Ashkenazi Jews? What is the inheritance pattern? What Factor?
Hemophilia C, autosomal recessive, factor XI.
What are the symptoms and treatment for Hemophilia C?
Mild bleeding symptoms and treated with Fresh Frozen Plasma for factor replacement.
What severe deficiency does NOT produce bleeding or pose as a surgical risk? Is there a treatment?
Factor XII deficiency (Hageman Factor), No treatment.
What would the screening tests look like for Factor XII deficiency?
Normal PT and a prolonged APTT
What factor deficiency is most often diagnosed at birth because most common symptom is umbilical stump bleeding?
Factor XIII (Fibrin Stabilizing Factor) Deficiency.
What would the screening tests for factor XIII look like?
What factor deficiency is autosomal recessive, where the factor is vitamin K deficient and produced in the liver? Also may be influenced by Coumadin
Factor VII deficiency.
What would the screening tests look like for Factor VII deficiency? How is it treated?
Abnormal PT and normal APTT. Treated with FFP, prothrombin concentrates, vitamin K and factor VII.
What factor deficiency is autosomal recessive and can be acquired in amyloidosis? What are the screening results? How do you treat it?
Factor X deficiency, Both normall APTT and PT with normal platelet function screen, treat with FFP, prothrombin complex concentrates and Vit. K.
What deficiency is associated with a protein that functions as a cofactor that binds with Prekallikrein and factor XI to facilitate activation by factor XII? What is the treatment?
High molecular weight kininogen deficiency; No treatment necessary.
What is Prekallikrein?
A contact factor that complexes with high molecular weight kininogen and is cleaved by factor XII to produce kallikrein.
What rare congenital disorder causes an isolated prolonged APTT but is not associated with a bleeding tendency?
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