COAG Review

1. COAG Review

2. BOR Exam Thrombocytes and hemostasis will comprise 29% of the subtest and 5% of the total exam (ASCP).

3. NCA EXAM • 9 questions on 100 question test • 2 recall • 5 application • 2 analysis

4. Basic Cascade HMWK PK XII XI IX VII Ca+Ca+ TT PF3 VIII X Ca+ PF3 V II I XIII

5. There are many cascades to use. Some are highly complex and contain the anticoagulant aspects of the pathway as well as clotting components. Be sure you can use the pathway you choose to learn.

6. Correction Studies There are many questions that will require you to know what is in aged serum and adsorbed plasma. Aged serum 2 7 9 10 11 12 Adsorbed plasma 1 5 8 13 11 12

7. Correction study questions will also use normal plasma, and corrections with factor deficient plasma. The next several slides will be examples of registry questions that require a an understanding of the Pathway and correction studies

8. Example 1 • A 56 year old woman was admitted to a hospital with a history of moderate to severe bleeding tendency of several years duration. Epistaxis and menorrhagia were reported. Prolonged APTT was corrected with fresh normal plasma, adsorbed plasma, and aged serum. Deficiency of the following is most likely? • Factor XII • Factor VIII • Factor XI • Factor IX

9. Example 2 • A patient has a history of mild hemorrhagic episodes. Laboratory results include prolonged PT and APTT. The abnormal APTT was corrected by normal and adsorbed plasma, but not aged serum. Which of the following coagulation factors is deficient? • Prothrombin • Factor V • Factor X • Factor VII

10. Example 3 • A patient with a history of frequent mild bleeding episodes has a normal PT and a moderately prolonged APTT, which is corrected by the addition of each of the following: normal plasma, factor VIII deficient plasma, factor IX deficient plasma. Which factor assay(s) should be run? • VIII • IX • XI and XII • None; a circulating inhibitor is present

11. Know your factor groups. What factors are labile, and how long are labile Factors stable at room temp? What factors are vitamin K dependent, produced in the liver, affected by coumadin, and are stabile at room temp? What factors are considered “contact factors”?

12. Example • Coagulation factors affected by coumadin drugs are: • VII,IX, and X • I, II, V, and VII • II, VII, IX, and X • II,V and VII • Which of the following factors is considered to be labile? • II • V • VII • X

13. Labile factors I V VIII and XIII Liver dependent, Vitamin K dependent, Stable, and affected by Coumadin II VII IX and X Contact factors PK HMWK XI XII

14. Know your factor deficiencies, especially the hempohilias (A,B and C). Hemophila A Factor VIII Hemophilia B Factor IX Hemophilia C Factor XI Be familiar with the clinical presentations and lab findings.

15. Example • Which of the following is most useful in differentiating hemophilias A and • B? • Pattern of inheritance • Clinical history • APTT • Mixing studies (Substitution study) • A hemophiliac male and a normal female can produce a: • Female carrier • Male carrier • Male hemophiliac • Normal female

16. Know Von Willebrand’s disease. You need to know the clinical presentation and lab findings. Von Willebrand’s Hemophilia A Deficiency VIII:vWF VIII:C VIII: AHF Inheritance Dominant: autosomal Recessive: Sex-linked Clinical Bleeding Gums, GI, Mucous Hemarthrosis,muscle membranes visceral Lab tests BT/PFA100 A N Clot retraction N N Plt count N N Ristocetin A N PT N N APTT A A VIII A A vWF:AG A N

17. Example The following lab data were obtained from a 40-year old woman with a long history of abnormal bleeding: PT Normal APTT Prolonged VIII coagulant activity Decreased VIII-related antigen Markedly decreased Plt count Normal Bleeding Time Prolonged Which of the following disorders does this woman most likely have? a.classic hemophilia b.Von Willebrand’s disease c. Christmas disease d. DIC

18. Know the role of platelets in coagulation. • Topics frequently covered in review books include • Reagent added to platelet aggregation studies to test • for release of dense granules as well as aggregation • -firefly luciferase- (lumiaggregometry) • When performing plt aggregation studies, the instrument • should be set on 100% transmittance using patient plt • poor plasma • Plt aggregation pattern expected from patient with Bernard- • Soulier if ristocetin is the agonist- • This would be a flatline pattern or no aggregation • On patient’s plt rich plasma sample used to set 0% • baseline for aggregation studies, what should the plt count • be? 300 x 109/L (we use 250+ or – 50)

19. 5. What is the most common cause of an abnormality in hemostasis – quantitative abnormality of platelets 6. Plt aggregation is dependent in vitro on the presence of calcium ions 7. A bleeding time is used to evaluate the activity of –platelets This would also be true for PFA100 studies 8. A patient taking aspirin for pain would have an abnormal bleeding time. 9. In Von Willebrand’s disease, platelets give an abnormal aggregation in the presence of – ristocetin 10. In the performance of a bleeding time test, the blood pressure cuff should be inflated to – 40mm Hg

20. Know the collection and storage requirements for Coagulation –examples of questions 1. Anticoagulant of choice – 3.2% sodium citrate Order of draw – red, blue, purple 2. Thawing of platelet-poor plasma that has been stored At -40°C should be perfomred at 35-38 °C 3. Collection on patients with Hcts <20 and >55% Formula to adjust anticoagulate C=1.85 X 10-3(100-H) x V C= volume of sodium citrate in ml V=volume of whole blood H= hematocrit %

21. 4. Specimen for APTT in sodium citrate is collected at 9:30 am and allowed to remain at room temp until 3:30- How will this effect results-Prolonged due to loss of VIII 5. The tech notes an APTT was at room temp for 3 hours. The tech should – request a new sample 6. Blood for coag studies must be centrifuged - with the top on. 7. A sample was drawn in sodium citrate. It has approximately 90% of the expected amount. The specimen should be deemed - acceptable

22. There are several questions in current review books • That relate to quality control. Need to know basic • QC procedures and guidelines. Examples…. • Mean of PT control is 12.2. One SD is 0.2. According to • Gaussian distribution, 95% will fall in what range • Upward trend observed over 6 days in QC plot for PT on a • Photo-optical analyzer. This indicates-loss of precision • Abnormal QC is out for PT and APTT. The normal control • is in range. The appropriate action is – Repeat abnormal • control on a new bottle before proceeding.

23. Know basics of testing procedures (photo-optical vs • mechanical) and basic instrumentation guidelines. • Examples • Specimen from a patient with severe jaundice. PT on a • photo-optical analyzer is 7.4 seconds. The tech should- • Perform test on a electromechanical instrument • Patient with increased cryoglobulin is evaluated for bleeding • disorder. Which instrument will give accurate results • - electromechanical • On automated analyzers, duplication of normal results is not • appropriate because-lab can document precision to reflect • analyzer performance

24. Five preoperative patients and QC for APTT were • prolonged on an optical density analyzer. Results were • confirmed using an alternate method (mechanical).What would be explanation- reagent contamination • If the automatic pipette is left on after each use on an • electromechanical system what will happen-probe will • fall into reactor when you pick up next sample

25. Be familiar with the basic tests and what information they • Provide. Examples… • The PT requires that patient citrated plasma be combined • with---Ca++ and thromboplastin • A bedside test for monitoring heparin is—ACT • The APTT monitors – Heparin therapy • Plasma is diluted in a fibrinogen-activity determination to • decrease the --- influence of inhibitors • 5. Common test for monitoring Coumadin --PTINR

26. Questions dealing with Factor XII • Patient has a normal PT and a prolonged APTT using • a kaolin activator. The APTT corrects to normal when the • incubation is increased---This suggests Hageman factor (XII) • Factor XII is associated with a negative bleeding history • Factor XII is involved in the following: • Activating C1 to C1 esterase • Activation of Plasminogen • Activation of XI

27. DIC • Know the clinical presentations and lab findings in DIC. • Clinical Manifestations • Hemmorhaging – usually from 3 unrelated sites • Petechiae, purpura, gangrene, wound bleeding, • veni-puncture bleeding, subcutaneous hematoma • Microthrombi • End-organ dysfunction

28. DIC • Lab Findings • Hypofibrinogenemia • Abnormal PT • Abnormal APTT • Abnormal Thrombin Time • Abnormal PLT count • Abnormal tourniquet test and clot retraction • Positive FDP, Ddimer, and protamine sulfate • ATIII consumption • Leukocystosis • Schistocytes

29. Some conditions associated with DIC • Obstetric accidents • Intravascular hemolysis • Septicemia • Viremia (varicella) • Leukemias – Acute Promyelocytic • Malignancy • Burns • Crush injury

30. Examples of DIC questions and FDP questions • A patient with severe DIC has an FDP of >200 ug/ml • and a clottable fibrinogen of 50mg/dl. The fibrinogen level • may have been affected by -- Interference from elevated • FDP products • A test used to monitor streptokinase therapy is – fibrin • split products • In latex agglutination method for determining serum • fibrin/fibrinogen degredation products, which of the • following can be a cause of false positive results – • The specimen is collected in a regular red-top tube instead • of special FDP tubes. • 4. Acute DIC is characterized by: -hypofibrinogenemia

31. 5. A patient develops severe unexpected bleeding and the following test results are obtained: PT and APTT Prolonged PLTS 50 x 10-3/uL Fib 30 mg/dl FDP Increased Most probable cause – DIC

32. Know what effect inhibitors will have on basic coag • Tests, and how to identify and confirm them. • Examples • Patient has a normal PT and a prolonged APTT. To • determine if the prolongation is due to a factor deficiency • or a circulating inhibitor the CLS should-Mix 1 part • patient plasma with 1 part normal reagent plasma and repeat • APTT • A patient's thrombin time is 25.5 seconds. The control is • 11.5 seconds. The patient’s plasma is mixed with an equal • part of normal plasma. The thrombin time is rerun and is • 28 seconds. This indicates----circulating anticoagulant • Plasma from a patient with a Lupus inhibitor can show- • A prolonged APTT and a normal PT • An abnormal APTT that does not correct when mixed with • equal parts of normal plasma indicates – a circulating • inhibitor

33. Thrombin time is used to detect dysfunctional fibrinogens and • Is very sensitive to anticoagulant therapy. Examples of • questions • A 54 year old man was admitted with pulmonary embolism • and given streptokinase. What would be most useful in • monitoring this therapy? • a. APTT • b. Bleeding time • c. PT • d. Thrombin time • All of the following cause an increase in the thrombin • time except: • a. hypofibrinogenemia • b. increased FDP • c. heparin therapy • d. prothrombin time

34. Anticoagulant Therapy • Coumadin degrades vitamin K and thus lowers factors II,VII, • IX, and X • Heparin binds to ATIII to inhibit thrombin • Examples of questions: • The first step in the determination of functional ATIII is to • a. neutralize plasma ATIII • b. Neutralize thrombin with test plasma • c. incubate plasma with anti-ATIII • d. Precipitate ATIII with plasma

35. Biological assays for ATIII based on inhibition of • a. Factor VIII • b. Heparin • c. serine proteases • d. Anti-ATIII globulin • Decreased response to heparin therapy may be caused by decreased • levels of • a. ATIII • b. Platelet factor 4 • c. Factor XIIII • d. thromboxane • Enzymes measured in chromogenic substrate assays are of what class? • Serine proteases • Lysine arginases • Carboxyl anhydrases • Lysases

36. The last examples are in a miscellaneous category. • Questions on these types of topics were rare in the review books. • Clot incubated at 37C dissolves in 24 hours you suspect what- • Fibrinolysis • Low fibrinogen level • Factor VII deficiency • Thrombocytopenia

37. MISC continued • Results on newborn were • PT 12.8 (9.5-14.5) • APTT 34.5 (20-35 sec) • TT 14.0 (9-13) • Fib 380 mg/dl (200-400) • This suggests • a. Factor VII • b. Normal newborn results • c. hyperfibrinogenemia • d. Vitamin K deficiency • Most potent plasminogen activator in contact phase is- • kalikrein

38. Misc Continued • Protein C and S are part of anticoagulant process. • Protein C with the cofactor protein S inactivate V and VIII. • Deficiencies of either will increase the risk of thrombosis. • Factor XIII- Associated with delayed bleeding and 5M • urea solubility test