A 35 yr old lady with normal PT and increased aPTT. 2 year back, she was operated for cholecystectomy & did not have any bleeding episoe. What is next investigation for clinical diagnosis –
Correct Answer: Anti viper venom assay
Description: Ans. is 'b' i.e., Anti viper venom assay The only clue given in the question is patient with prolonged APTT and no clinical bleeding.First we, look at the causes of isolated prolongation of APTT.Causes of isolated prolongation of PTHeparinLupus anticoagulantCoagulation factor deficiency (factor VIII, IX and XI, XII, prekallikrein, high molecular weight kininogen (HMWK)Specific coagulation factor inhibitors (antibodies against factor VIII or IX)Now we look for those causes of prolonged APTT which are not associated with bleedingNow we move on to the options and find out which among them will cause prolongation of PTT with no bleeding. Factor VIIIc assay:-Factor VIIIc or intrinsic factor VIII can be ruled out because its deficiency is associated with bleeding.Platelet a2sre2ation testsPlatelet aggregation test measures platelet functionAny defect in platelet function will cause clinical bleedingPlatelet function defect does not affect PTT (it affects bleeding time, BT)Ristocetin co-factor assayRistocetin co-factor assays are used to detect Von Willebrand's diseaseVon wile brands disease cause prolongation of PTT but it is also associated with clinical bleeding so it can be ruled out.Russel viper venom test (Dilute Russel viper venom test) (dRVVT)Dilute Russel viper venom test is one of the test to detect lupus anticoagulant.Lupus anticoagulant is associated with prolongation in PTT and thrombosis (no bleeding)Lupus anticoagulantLupus anticoagulants are acquired inhibitors directed against phospholipid binding proteins and are a common cause of APTT prolongationIn Vivo,Lupus anticoagulant do not interfere with coagulation factor complex formation on the platelet surface and are not usually associated with bleeding tendency, instead they are frequently associated with thrombosis.In Vitro,This prolongation results in paradoxical prolongation of phospholipid based clotting assays such as PTT, kaolin clotting time and Dilute Russel viper venom antibody (DRVVT testing).A panel of test is required to confirm the presence of lupus anticoagulantThese are:-PTTKaolin clotting timeDilute Russel viper Venom test (DRVT)These are phospholipid dependent testsWe have already discussed thatLupus anticoagulant act against phospholipids and in vitro this inhibition leads to prolongation of phospholipid dependent assays.Follow up testing is performed to confirm or exclude the presence of lupus anticoagulant:- These may include:-Mixing studyAn equal volume of patient plasma is mixed with normal pooled plasma and a PTT or DRVVT is performed on this mixture. The basic principle is that the normal plasma contributes a sufficient amount of clotting factor to correct for a factor deficiency.A mixing study that corrects the APTT is characteristic of a coagulation factor where as one that does not correct indicates a factor inhibitor.Correction neutralization (with phospholipids)An excess of phospholipid is added to the patient sample and APII, DRVVT is performed.The basic principle behind this is that lupus anticoagulant is directed against phospholipid. Hence phospholipid dependent assays are prolonged.When excess phospholipid is added it overcomes the LA inhibition and corrects the test
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