THROMBOSIS AND BLEEDING

Transcription

1 THROMBOSIS AND BLEEDING Klara Gadó MD. PhD. Senior Professor of Internal Medicine Semmelweis University, Budapest

2 What is thrombosis? formation of a blood clot in a blood vessel Blood can not flow Organ supply is not appropriate, Organ damage, necrosis Blood clot. Coloured scanning electron micrograph (SEM) The red blood cells (erythrocytes, red) are trapped in filaments of fibrin protein (grey).

3 Conditinons promoting clot formation Clot forms when circulation to a particular part of the body is abnormally sluggish damage has been done to a blood vessel, there is an imbalance between clotting and bleeding factors. bleeding thrombosis

4 How common is DVT? every year about 1 in 5,000 people are diagnosed with DVT. The risk is even greater among older people. affects approximately 200,000 Americans per year Source: Fowkes FJI, Price JF, Fowkes FGR, et al. European Journal of Vascular and Endovascular Surgery. 2003; 25: 1-5.

5 What are the consequences of DVT? Leg ulcer is an extremely common problem affecting about 1-2% of the general population in the UK. Postthrombotic syndrome

6 What are the consequences of DVT? if the clot breaks free and travels through the veins where it can reach the lungs, obstructing the pulmonary artery or its branches, which supply the lungs with blood This is pulmonary embolism

7 Clinical assessment of VTE (venous thromboembolism)

8 Symptoms of deep vein thrombosis in the lower leg swelling erythemia (redness) warmth in the area caused by capillary congestion. Pain stiff and shiny skin

9 Signs of deep vein thrombosis in the lower leg Physical examination: Homans sign: development of pain in the calf or popliteal region on forceful dorsiflexion of the ankle with the knee in flexed position. sensitivity 13 to 48% specificity from 39 to 84%

10 Examination of Homans sign How to perform? Flex knee slightly; Dorsiflex foot

11 But! In the 50 % of cases people with DVT do not get any symptoms!!!!!

12 ultrasound Diagnosis of DVT Longitudinal section Cross section

13 Diagnostics DVT in the lower limb, color Doppler,

14 Pulmonary embolism about 30,000 people die each year in the United States Often post-mortem diagnosis

15 Pulmonary embolism incidence of the disease: / inhabitant/year 10 % of cases leading to immediate death mortality among survivors: 30 % with proper treatment this can be lowered to 10 % Dg: spiral CT, echocardiography

16 Symptoms of pulmonary embolism sudden, severe CHEST PAIN DYSPNEA (difficulty BREATHING) diaphoresis (breaking into a cold sweat) HYPOTENSION (low BLOOD PRESSURE) TACHYCARDIA (rapid heart rate) TACHYPNEA (rapid BREATHING)

17 ECG signs of PE The most common ECG finding is sinus tachycardia, the "S1Q3" pattern of acute cor pulmonale is classic (only occurs in about 10%) A large S wave in lead I, a Q wave in lead III, indicates acute right heart strain.

18 Pulmonary embolism COMPUTED TOMOGRAPHY (CT) SCAN, MAGNETIC RESONANCE IMAGING (MRI), pulmonary angiography, ventilation/perfusion scan echocardiography.

19 CT image of pulmonary embolism Thrombosis and bleeding, Semmelweis University, september, 2011

20 Ventillation/perfusion scan image of pulmonary embolism Lung scintigraphy is an indirect imaging method which non-invasively visualizes the perfusion defect caused by an embolus the procedure is highly sensitive and easily detects even small embolisms on a subsegmental level. coupled with a ventilation scan specificity improves a typical mismatch defect caused by pulmonary embolism.

21 Laboratory findings D-dimer test Bedside test

22 D-dimer test D-dimers are specific cross-linked fibrin derivatives product of plasmin-mediated fibrinolytic degradation. marker of fibrinolytic activity. The D-dimer assay can be used as a rule out test

23 Non-pathological conditions associated with elevated D-dimer titres include: Age (healthy elderly people) Cigarette smoking Functional impairment Post-operatively Pregnancy Race (e.g. African Americans)

24 Pathological conditions associated with elevated D-dimer titres include Acute coronary syndromes Acute upper gastrointestinal haemorrhage Aortic dissection Arterial or venous thromboembolism Atrial fibrillation Consumptive coagulopathy DIC Infection Malignancy Pre-eclampsia Stroke Superficial thrombophlebitis Trauma

25 D-dimer & VTE The D-dimer test is a marker of blood clotting activity and is not diagnostic of VTE. When used appropriately the D-dimer test helps rule out VTE if the test is negative and the chance of the patient having a VTE is relatively low.

26 Risk factors of thrombosis Thrombosis and bleeding, Semmelweis University, september, 2011

27 Risk factors Thrombophilia a group of abnormalities where there is a tendency for the occurrence of thrombosis, may be classified as inherited or acquired

28 Aquired risk factors Persistant Advancing age Malignancy Antiphosphilipid antibodies Prior history of VTE/PE

29 Aquired risk factors Transient Recent surgery Recent trauma Pregnancy, labour Prolonged immobilization (bedrest, travelling, leg fracture) Comorbities (heart failure, nephrotic syndrome) Drugs (oral contraceptives, chemotherapy hormon replacement therapy)

30 Inherited risk factors Antithrombin deficiency Protein C and S deficiency Factor V Leiden mutation Factor II G20201A gene mutation

31 POSSIBLE INDICATORS OF THROMBOPHILIA Thrombosis at early age (under 50) Thrombosis at unusual sites Thrombosis recurrence Thrombosis developed by mild provoking factor Habitual abortion, miscarriage, still-birth

32 MODERN TREATMENT OF VTE

33 Post-surgical TROMBOPROFILAXIS No thrombocyte aggregation inhibitor 1 week before surgery Changing vitamin K antagonist to LMWH Na-heparin 12 hours before operation EDA hours after LMWH LMWH can be given 4 hours after intervention

34 IN CASE OF RENAL INSUFFICIENCY need for decreasing heparine dose practical to give UFH

35 Monitoring of the treatment Vitamin K antagonist: Measuring INR Monitoring heparin therapy: Measuring aptt Monitoring LMWH efficiency: anti-xa activity Obes patients on pregnant women Renal impairment

36 THE SIDE-EFFECTS OF HEPARIN I. HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) OSTEOPOROSIS ALOPECIA

37 THE SIDE-EFFECTS OF HEPARIN II. HIT 5 days after the beginning of the therapy thrombocytopenia + thrombosis Therapy: thrombocyte prohibited give direct thrombin inhibitors (lepirudin) Monitoring the number of thrombocytes during the therapy

38 LMWH self-injection neat therapy skilling of patients

39 Coumarin (warfarin, Syncumar) Some aspects: narrow therapy range Strong plasma protein binding Appropriate dose Starting with a small dose Starting: always overlapping with heparin Frequent control measuring INR Education (diet, medicines)

40 COUMARIN NECROSIS In the beginning of the therapy More frequent with Protein C absence Histology: fibrinoid thrombus in small veins Profilaxis: low starting dose, heparin protection

41 Bleeding disorders Thrombosis and bleeding, Semmelweis University, september, 2011

42 Classification of bleeding disorders Congenital Coagulation factor deficiency Aquired Consumption DIC Abnormal synthesis of coagulation factors Liver diseases Iatrogenic Overdosing anticoagulants Antibodies against coagulation factors toxic

43 Congenital Bleeding disorders Coagulation factor deficiency Hemophilia A (fviii) Hemophilia B (fix) Von Willebrand s disease

44 Hemophilia A Incidence: 1: Factor VIII is synthesized by the liver. It circulates in plasma in a form bound to a transport protein known as Von Willebrand factor (VWF).

45 Genetic aspects The gene for factor VIII is located on the long arm of chromosome X.

46 King s disease The Tsarevich Alexis had suffered from hemophilia, Queen Victoria

47 Clinical aspects Severe hemophilia A : in 30 to 40% of cases. The most common hemorrhagic episodes consist of: hemarthrosis: 70%, (joint deformity) subcutaneous or intramuscular hematomas: 10 to 20%, bleeding in the urinary tract, nasal and gastrointestinal mucosa, and intra-abdominal organs: 10 to 20%. Gastrointestinal and central nervous system hemorrhagic accidents are potentially life-threatening,

48 Screening for mutations Numerous mutations responsible for hemophilia A have been described screening techniques to characterize patients, carriers make prenatal diagnosis 1/3 of patients de novo mutation in a family hitherto unaffected by the disease.

49 Amniocentesis Usually performed weeks Risk of fetal death estimated as 1:200

50 Laboratory findings Prolonged PTT Normal PT Normal bleeding time Normal platelet count

51 Factor levels Factor activity Mild 5-25% Moderate 2-5% Severe 1% PTT prolonged only if activity 25% Spontaneous bleeding: 5%

52 Treatment replacement therapy giving or replacing the clotting factor that is too low or missing. Concentrates of the clotting factor are infused, or injected, directly into the bloodstream. The specific factors used to treat hemophilia are: Factor VIII for hemophilia A Factor IX for hemophilia B The activity level for factor VIII needed to ensure clotting is around 30%.

53 Treatment Replacement therapy can be used: To prevent bleeding (prophylactic or preventive therapy) To stop bleeding when it occurs, on an asneeded basis (demand therapy) The type of treatment you receive depends on several things, including whether you have mild, moderate or severe hemophilia.

54 Subcutaneous hematoma Epidural hematoma gingival bleeding

55 Joint deformity Thrombosis and bleeding, Semmelweis University, september, 2011

56 Inhibitors Antibodies develop against clotting factors Examining the presence of inhibitors Mixing studies Patient : normal plasma mix: 1:1 If: aptt has normalized means: factor deficiency apti does not normalized means: inhibitor is present

57 HEMOPHILIA B FIX deficiency, Christmas-disease More scarce, incidence 1:50000 difference: only with special laboratroy tests Coding gene on chromosome X, near to gene of fviii, much smaller gene than gene fviii Treatment: IXf concentrate Needed scarcer (IXf T 1/2 longer) Dose calculation (wanted % - actual %) x bwkg = Unit Thrombosis and bleeding, Semmelweis University, september, 2011

58 Therapy of the future: gene therapy Genes of clotting factors are taking into liver cells

59 Von Willebrand disease vwf is a large multimeric molecule Role: protecting fviii Platelet binding to endothel

60 Classification 1. vwf protein 2. Inappropriate vwf function 3. No vwf : severe bleeding

61 Clinical signs Bleeding during surgery Postoperative re-bleeding

62 Diagnosis Platelet count may be decreased Abnormal bleeding time fviii activity decreased Ristocetin-induced platelet aggregation decreased vwf ag vwf activity decreased Normal aptt, PT Special tests

63 therapy Desmopressin (DDAVP), VIIIf concentrate cryoprecipitate antifibrinolytics platelet

64 Aquired coagulopathies

65 Aquired coagulopathies More frequent Vitamin K dependent coagulation factor deficiency Liver disease malabsorption Disseminated intravascular coagulation

66 Liver disease Vitamin K dependent coagulation factor deficiency AT III, vwf aptt, PT Liver biopsy is dangerous Platelet count

67 THANK YOU FOR YOUR ATTENTION