1. Dr Narisha Ramparsad Department of Haematology and Molecular Medicine
VENOUS THROMBOSIS
Dr Narisha Ramparsad
Department of Haematology and Molecular Medicine

2. Normal haemostasis Ensures fluid state of blood in vasculature
Prevents blood loss – site of injury – by forming haemostatic plug
Clot removal – when healing is complete

3. Overview of Haemostasis
THROMBOSIS
BLEEDING

4. Definitions
A blood clot that forms in a blood vessel or within the heart and remains there is called a thrombus. A thrombus that travels from the blood vessel or heart to another location in the body is called an embolus, and the disorder, an embolism. For example, an embolus that occurs in the lungs is called a pulmonary embolism.
Sometimes, a piece of atherosclerotic plaque, small pieces of tumor, fat clumps, air, amniotic fluid, or other materials can act in the same manner as an embolus. (MEDLINE PLUS)

5. Pathogenesis -Thrombosis
Normally - balance between clotting and bleeding
With thrombosis - imbalance with procoagulant state manifesting
Risk increases when > 1 risk factor present
Venous thrombi – fibrin & RBCs mainly, leucocytes & plts also present
Virchow’s triad 1) vessel wall damage
2) blood flow (stasis)
3) hypercoaguability of
blood
Venous thrombosis can affect any part of venous system but deep veins most commonly affected.

7. Acquired Risk Factors Malignancy Presence of a central venous catheter
Surgery, especially orthopedic
Trauma
Pregnancy
Oral contraceptivesHormone replacement therapyTamoxifen
Immobilization
Congestive failure
Antiphospholipid antibody syndrome
Myeloproliferative disorders Polycythemia vera,Essential thrombocythemia
Paroxysmal nocturnal hemoglobinuria
Inflammatory bowel disease
Nephrotic syndrome
Hyperviscosity e.g Waldenstrom's macroglobulinemia, Multiple myeloma
Marked leukocytosis in acute leukemia
Sickle cell anemia

8. Acquired Risk Factors NB in South Africa – effect of HIV
Decrease Protein S, Protein C
Increase Factor VIII

9. Inherited Risk Factors
Factor V Leiden mutation
Prothrombin gene mutation
Protein S deficiency
Protein C deficiency
Antithrombin (AT) deficiency
Rare disorders: Dysfibrinogenemia

10. Coagulation Cascade – Inherited Risk factors – thrombosis

11. Venous thromboembolism (VTE)
VTE = Deep Vein Thrombosis (DVT) and/or Pulmonary Embolism (PE)
Incidence increases with age
117 cases/
Increasing health problem – prevention important, potentially fatal

12. VTE

13. VTE
Thrombosis commonly occurs in deep veins of limbs. Can also affect superficial veins
Venous system leg – 2 important categories deep calf vein involvement only proximal vein thrombosis (involving popliteal, femoral or iliac veins) – give rise to clinically significant PE
Pulmonary emboli ( majority arise from deep veins of leg >90%)
Other sources of PE include – upper extremity thrombosis, deep pelvic veins, renal veins, IVC

14. DEEP VEINS OF THE LEG

15. DEEP VEIN THROMBOSIS – clinical features
Leg pain, swelling, tenderness, palpable cord
(thrombosed vessel), phlegmasia cerulea
dolens in occasional patients.
Non specific signs and
symptoms.

17. Differential Diagnosis DVT
Cellulitis
Popliteal cyst
Lymphatic obstruction
Muscle strain/tear
Direct twisting injury to leg
If think about DVT – MUST objectively exclude

18. Pulmonary Embolism – Clinical Features
Symptoms variable
Transient Dyspnoea, tachypnoea
Tachycardia
Pleuritic chest pain, cough, haemoptysis,
CVS collapse with hypotension, syncope ( massive pulmonary embolism)
Clinically silent
Clinical features are non specific
ONCE again must objectively exclude

19. Laboratory investigations
D-Dimer assay
Compression ultrasound(DVT)
Venography (DVT)
Spiral CT (highly sensitive for PE
MRI
Work up for thrombophilic state when confirm diagnosis

21. Clinical course
Untreated proximal vein thrombosis – potentially lethal – fatal PE
Extension of thrombus proximally
Post thrombotic syndrome frequent complication of deep DVT. Heaviness, swelling cramps, itching, ulceration
Chronic thromboembolic pulmonary hypertension.

22. Treatment – Anticoagulant Therapy
Heparin: Unfractionated or Low Molecular Weight Heparins e.g Enoxaprin(Clexane), Dalteprin,
Fondaparinux
Vitamin K antagonists e.g Warfarin
Oral anti Xa (clinical trials)
Direct thrombin inhibitors

23. Initiation of treatment
Must cover with Clexane when initiating Rx with Warfarin – Why? ( short T1/2, Protein C) – relative prothrombotic state

24. Treatment – how long? Individualise each case
Look at risk factors present
Transient vs permanent vs no risk factors
1st episode vs recurrent thrombosis
Reassess
D-Dimer levels
Risk –Benefit ratio of anticoagulant therapy

25. Treatment – how long ?
First onset ,transient risk factor – 6 months , recheck D-Dimer levels . If raised continue ? Indefinite therapy.
First onset, idiopathic thrombosis – consider life long Warfarin. Reassess risk-benefit ratio
Recurrent DVT – indefinite anticoagulation
Patients with APL antibodies or 2 more inherited risk factors – 12 months anticoagulation and reassess

26. Treatment how long
First episode thombosis – with deficiency of natural anticoagulants e.g. antithrombin, Prot C, Prot S or FVLeiden/Prothrombin gene mutation – 12 months and reassess ? indefinite therapy

27. Side effects of anticoagulant therapy
Bleeding
Heparin Induced thrombocytopenia and thrombosis
Heparin induced osteoporosis, increased transaminase levels, hypersensitivity reactions e.g. necrosis, alopecia, hyperkalaemia

28. Treatment – Thrombolytic therapy – When?
Indicated in patients with PE – haemodynamically unstable , evidence of R ventricular failure
Threatened limb in setting of DVT

29. Prophylaxis – venous thrombosis
Important to identify those patient at increased risk of thrombosis
Prevention
Use of LMWH, compression stockings
Awareness – patients and health care professionals

30. CONCLUSION
Venous thromboembolism – major cause of morbidity and mortality
Identify risk factors early -institute prophylaxis
Prophylaxis imperative measure to decrease incidence of thrombotic events
If suspect thrombosis must objectively test
Duration of treatment – varies -individualise