Clinical hemostasis. Bodó Imre

Transcription

1 Clinical hemostasis Bodó Imre

2 Phases of blood clotting I. Primary hemostasis (vascular + PLT) II. Secondery heamostasis (fibrin clot) III. Kontrol system (stopping the cascade) IV. Fibrinolysis

3 Felületaktiválás FXI FXIa FIX FIXa FVIIIa Pl Tenase Ca ++ FVIIa TF Thrombin Xa VIIa IXa Ca++ FVII Érfalsérülés TF FIX TF FVII FVIII FX FV FXa FVa Pl Ca ++ FX Prothrombinase Prothrombin Thrombin FXIII Fibrinogén Fibrin FXIIIa Fibrin (keresztkötött)

4 aptt PT

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6 History Screening Bleeding symptoms Keep in mind: Procedures/trauma (hemostatic stress) Operations, Fractures Extractions OB/GYN Hx - Menses, deliveries etc. Timing Drugs (spirin!) Family history

7 HISTORY - TIMING Primary Secondary PLT /vwd Hemophilia Location Skin, mucus Deep tissue; m. muscle, joint Superficial Yes No scratch Petechia Yes No Echymosis Small, Large, deep superficial Hemarthros, Very rare Often muscle hematoma Post-OP Immediate Delayed

8 Basic screening assays CBC Prothrombin time(pt) ctivated partial thromboplastin time (aptt) Thrombin idő Bleeding time (Ivy) Patient:Normal 1:1 mixing study

9 Before interpreting results: Nem technikai eredetű-e a rendellenesség? Blood drawing!! Hematocrit Heparin!!

10 Mixing studies - I Control 1. Patient 2. Patient B B B B + B B B B B B B B Normál Prolonged Prolonged Normal

11 Mixing studies- II Control Patient Control 1:1 P:NP B B + B B B B B B B B PT / PTT Normal Prolonged Normal Normal

12 Mixing studies- III Control Beteg Control 1:1 P:NP B B B B B B + B B B B B B B B B B PT / PTT: Normal Prolonged Normal Prolonged

13 PT apti TI ll screening assays normal Patient does not have a bleeding problem primary hemostasis (PLT; vascular) is at fault von Willebrand disease XIII-as factor deficiency! α-2-ntiplazmin deficiency PI-1 deficiency

14 PT apti TI Izolated PT prolongation NP corrects Hereditary - FVII def.- rare! cquired - K-vit. deficiency - Coumarin - Liver dz. NP does not correct cquired - FVII inhibitor Very rare!!

15 PT PTT TT Isolated PTT prolongation Hereditary NP corrects Hemophilia differencialdiagnózis! 1. FVIII 2. FIX 3. FXI 4. Contact phase probléms (FXII def.) no bleeding! 5. VWD - Vérzési idő megnyúlt!! NP does not correct cquired 1. Heparin 2. Lupus anticoagulant (L) - no bleeding! 3. FVIII (IX, XI, XII) inhibitor

16 PT PTT TT apti + PT is megnyúlt Hereditary NP korrigál Factor-hiány: Fib (I) II, V, X Kombinált faktorhiány: (V-VIII; vit-k-depend.) cquired Súlyos K vit. hiány Coumarin mérgezés Súlyos májbetegség FX-def. acquired () NP nem korrigál: cquired Heparin high dose Strong L DIC (FV or FX inhibitors rare)

17 PT apti TI Prolonged thrombin time Isolated Very rare! ntibodies to bovine thrombin no bleeding. (Occaisonally: FV cross-reaction but: PT, PTT is also prolonged) Dysfibrinogenemia (mild) long with apti and PT prolongation Heparin (and direct thrombin inhibitors) DIC (FDP) Hypo- or dysfibrinogenemia

18 Purpura

19 Wet purpura

20 Purpura

21 Large deep hematomas

22 Hemophilia

23 Thrombophilia and VTE Bodó Imre

24 Thromboembolic disorders Diagnosis is not possible on clinical basis alone objective modalities are paramount Doppler US / D-dimer Spiral CT (V/Q scan) Other (Pletismography, venography, angiography)

25 History DVT/PE Most important: provoking factors Trauma Surgery Immobilization (e.g. stroke, cast, > 3 day bedbound illness) Pregnancy, post-partum period Oestrogen 8 hour flights Obesity ge

26 History DVT/PE Underlying systemic illness? Malignancy Nephrotic syndrome IBD HIT Myeloproliferatív disorders PNH CHF trial fibrillation Hyperhomocysteinemia nti-phospholipid syndrome - L

27 Iatrogenic? History DVT/PE Thrombosis while on heparin? (HIT) Hydralazine, procainamide, phenothiazinok (secunder PL?)

28 Family history DVT/PE Oligogenic hereditary disease? T-III deficiency PC-deficiency PS-deficiency PC-resistance (FV-Leiden) Prothrombin G Dysfibrinogenemia, plasminogen deficiency (rare!)

29 Examination of the pt with DVT Signs of post-thrombotic syndrome (leg ulcer?) Livedo reticularis Cyanosis? (cerdio-respiratory disorders?) Sings/symptoms of IBD (wt loss, pyoderma gangrenosum) Splenomegaly, hepatomegaly (myeloproliferative dz, liver dz)

30 Laboratory tests in the evaluation CBC of VTE patients Increased cell counts, eosinophilia, basophilia (myeloproliferatív dz; secondary polycythemia due to malignancy, etc.) Cytopenia (e.g. PNH), malignancy Smear (e.g. fragmentocytosis; leukoerythroblastic picture, basophilia) Elektrolits, liver- renal function tests Urinalysis nephrosis?

31 Thrombosis localization - venous Hereditary thrombophilias Malignancy Myeloproliferative disorders PNH IBD Nephrotic syndrome

32 Thrombosis localization - arterial terosclerosis Cocain, amphetamins, smoking Embólization (atrial fibrillation, endocarditis, myxoma, cholesterol embolizáció etc.) Paradox embolization Caisson disease TTP Vasculitis L, hyperhomoysteinaemia

33 Thrombosis localization venous+arterial L Hyperhomocysteinaemia HIT Myeloproliferative dz PNH Hyperviscosity (P. vera, Waldenström) Dysfibrinogenaemia, Paradox embolization

34 Venous thrombosis unusual V. lienalis V. portae V. mesenterica localization V. hepatica (Budd-Chiari syndrome) V. renalis Cerebral venous sinuses Upper extremity

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36 Visceral venous thrombosis Myeloproliferative dz PNH L IBD Daganatos betegségek Severe Recurrent Unusual localization ctive dz Young age

37 Unprovoked DVT - thrombophilia Thrombophilia testing: Young age VTE (< 50) Recurrent Unusual localization (mesenteric, vena portae, vena hepatica, cerebral sinus) Venous + arterial Hereditary defect: Young age VTE (< 50) Pozitive family history

38 Thrombophilia: acquired problem? Lupus anticoagulant/anti-phospholipid antibodies Hyperhomocysteinemia FVIII (> 150 %) OR 4,8 (vs <100) FIX FXI

39 Thrombophilia screening I waste of money Would only make sence if we could predict relapse this is not the case The lack of therapeutic consequence makes the test superfluous

40 Thrombophilia screening II Should be done for all DVT Multiple defects carry a high risk of recurrence Test results that have a high impact on treatment decisions: nti-phospholipid b (PS) Multiple defects T (??PC, PS??) deficiency Screening family memberscould help manage their pregnancy, OC decisions, etc.

41 VTE who to screen First unprovoked VTE < 50 y.o. Unprovoked or minor provocation: OC Flight Pregnancy Recurrent VTE in family history Unusual localization; consider additional testing: JK2 mutation PNH (flow cytometry test)

42 VTE whom not to screen rterial thrombosis entire panel not indicated. However: nti-phospholipid b R/O MPD (??JK2??) Provoked thrombosis, after maior surgery, or trauma event, or immobilization VTE in patients with an obvious systemic disease ctiv malignancy MPD HIT SLE check a-pl T only IBD Pre-eclampsia after week 36 Retinal vein thrombosis

43 DVT goal of treatment IMMEDITE Stop thrombus growth Prevent embolization (Limb-threatening ischemia (phlegmasia coerulea dolens): save the limb) LONG-TERM Prevent the next thrombotic event Prevent post-thrombotikus syndrome

44 Risk group Low-risk group Thrombophilia treatment: Treatment 3-6 months C Obvious temporary provocation + risk-adopted prophy - Fracture, cast immobilization - major surgery, other immobilization - gestation (pregnancy, post-partum)

45 Risk group High-risk group Thrombophilia treatment: 2 or more unprovoked TE treatment 1 unprovoked TE, but a life-threatening PE, or unusual lokalization 1 unprovoked TE genetic defect (e.g. FVL+FIIM) - T deficiency, (PC, PS) or PS Intermediate risk group Not fitting the other categories Long-term C Individual decisions

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