VENOUS THROMBOSIS

Dr Narisha Ramparsad

Department of Haematology and Molecular Medicine

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

Overview of Haemostasis

THROMBOSIS BLEEDING

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)

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.

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

Acquired Risk Factors

NB in South Africa – effect of HIV Decrease Protein S, Protein C Increase Factor VIII

Inherited Risk Factors

Factor V Leiden mutation Prothrombin gene mutation Protein S deficiency Protein C deficiency Antithrombin (AT) deficiency Rare disorders: Dysfibrinogenemia

Coagulation Cascade – Inherited Risk factors – thrombosis

Venous thromboembolism (VTE)

VTE = Deep Vein Thrombosis (DVT) and/or Pulmonary Embolism (PE)

Incidence increases with age 117 cases/100 000 Increasing health problem – prevention

important, potentially fatal

VTE

VTE

Thrombosis commonly occurs in deep veins of limbs. Can also affect superficial veins

Venous system leg – 2 important categories 1- deep calf vein involvement only 2- 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

DEEP VEINS OF THE LEG

DEEP VEIN THROMBOSIS – clinical features Leg pain, swelling, tenderness, palpable cord

(thrombosed vessel), phlegmasia cerulea

dolens in occasional patients.

Non specific signs and

symptoms.

Differential Diagnosis DVT

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

exclude

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

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

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.

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

Initiation of treatment

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

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

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

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

Side effects of anticoagulant therapy

Bleeding Heparin Induced thrombocytopenia and

thrombosis Heparin induced osteoporosis, increased

transaminase levels, hypersensitivity reactions e.g. necrosis, alopecia, hyperkalaemia

Treatment – Thrombolytic therapy – When? Indicated in patients with PE –

haemodynamically unstable , evidence of R ventricular failure

Threatened limb in setting of DVT

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

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