Coagulation Course: Lecture 3
DIAGNOSIS OF COGULATION DISORDERS Dr. Akram Al-Hilali 2009
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Does a patient have Bleeding diathesis? History taking should be careful. If history is suggestive, start with CBC, PT and PTT If pre-operative, delay surgery till results are out, when possible.
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Put results together Platelet
number is
normal. Platelet morphology is normal Interpret PT and PTT results. 4
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Platelet Function testing
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History suggestive: If platelet count is normal with normal PT and PTT platelet defect ought to be considered. Check blood film for unusually large or small platelets. Check screening test for function by PF100, if available. Otherwise check bleeding time. If abnormal then go for full platelet aggregation study. 08/06/14
THE THREE COAGULATION SCREENING TESTS TISSUE INJURY
CONTACT
THROMBOPLASTIN
XII
VII
VIIa
XI V
Prothrombin
TT
IX
VIII
Ca++ Phospholipid
PTT
PT
X
Thrombin FIBRIN
Fibrinogen
XIII
Dr.Akram Al-Hilali 1985
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BOTH PT AND PTT ARE NORMAL WITH BLEEDING HISTORY
Low platelet number and /or function defect Not a systemic disease (localized problem) Factor XIII deficiency
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ONLY PT IS PROLONGED Clear prolongation in a baby: Factor VII deficiency. Slight prolongation, in an adult, not on warfarin: Check liver function. Factor X Riyadh or FX Padua
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Factor X Riyadh Š 2007 Schattauer GmbH, Stuttgart542
Analysis of the novel factor X gene mutation Glu51Lys in two families with factor X-Riyadh anomaly Akram Al-Hilali1, Karin Wulff2, Hikmat Abdel-Razeq3, Khalida Abu Saud1, Fateh Al-Gaili1, Falko H. Herrmann2 1 Haematology Department, Laboratories, King Fahad Armed Forces Hospital, Jeddah- Saudi Arabia; 2 Institut fĂźr Humangenetik, Ernst-Moritz Arndt-University Klinikum Greifswald, Greifswald, Germany; 3 Hematology-Oncology Unit, Section of Hematology and Medical Oncology,
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ONLY PTT IS PROLONGED
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Male child, history of bleeding, clear prolongation: Hemophilia A or B. Older children and adults, mild mucous membrane bleeding or vague bleeding history: Possible von Willebrand’s disease. Factor XII or FXI deficiency Some cases of Factor X deficiency Mild cases of Factor V deficiency Acquired: like Lupus anticoagulant. 08/06/14
BOTH PT & PTT ARE PROLONGED
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Deficiency of one of the common pathway factors: II, V, X, Fibrinogen. Multiple coagulation defects. These are acquired conditions: Liver cirrhosis, vitamin K deficiency, DIC. Warfarin therapy After massive stored blood transfusion (dilutional coagulopathy). After streptokinase therapy
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COAGULATION FACTOR ASSAYS
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If only PT is prolonged start with FVII If FVII is normal do FX assay by PT base. If only PTT is prolonged start with FVIII, if normal go to FIX, if normal check XI, if normal check FXII. If normal check FX by PTT base. HMWK and Prekallekrein come at the end. Their assay is not usually available in hospital labs. Remember the mixing study if VIII and IX are normal, especially in females. 08/06/14
Early liver disease and low dose warfarin- Special consideration
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Only PT will be a little prolonged This is because of the short half-life of FVII, which affects only PT. PTT will start rising in advanced liver disease and will be very high in terminal cases (DIC) PTT will start rising with continued warfarin therapy, but will still not be as prolonged as PT. PTT could be very high in warfarin overdose. No need for PTT to monitor warfarin. INR is the test to go by. 08/06/14
HEPARIN EFFECT
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Only PTT may be prolonged in low doses and early sc heparin. With established heparin therapy PT will become prolonged, but always less than PTT. No need to check PT in heparin therapy. This condition is not expected to cause confusion with inherited disorders except when patient’s history is not known. 08/06/14
HOW TO DIAGNOSE VWD?
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The common type (Type I) will give mild prolongation of PTT and abnormal platelet function screen by PF100. Mild condition. Factor VIII assay is low, but rarely very low. vWF is low. Chromatography for vW multimers. Normal pattern, reduced concentration. By platelet aggregation studies: will show defect with ristocetin added. Type III- Severe condition. vW multimers and factor are not detectable. 08/06/14
PRE-OPERATIVE CHECKING
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Some surgical sub-specialties practice pre-operative coagulation screen. If to be done it should be early, to avoid delays of surgery. When result is clearly abnormal go through full investigation. Mild prolongations are a nuisance to all sides. Start by requesting a repeat sample. Remember liver disease! Always check mixing studies to be prepared for possibility of having to do surgery without delay. 08/06/14
UPS AND DOWNS IN COAGULATION RESULTS
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Unusual with clear prolongations. Pre-analytical factors. True mild and transient prolongations exist. Such findings may come after viral conditions. Remember that slightly prolonged screening test indicates around 50% factor level. 08/06/14
Mixing study
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Mixing with abnormal plasma for quick differentiation between FVIII and FIX deficiencies. Mixing with normal plasma is a special technique. Most hospitals do simple mixing. This kind of study is not standardized and does not rule out delayed-action inhibitors. Many results are ambiguous and cause confusion. 08/06/14
Mixing study- Refined technique
1:4 mix with incubation, if prolongation is <10” higher than normal upper limit. 1:1 mix with incubation if >10” Failure to correct the 1:1 mix indicates strong inhibitor. ppPTT ̶ Mix PTT X100 ppPTT – CNP PNP* PTT
>70% correction: Factor deficiency. 58-70% correction: Borderline. Repeat later. <58% :Inhibitor. * [CNP: Commercial Normal Plasma. PNP: Pooled Normal Plasma]
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