Pathology
Haematology
Which of the following is the most common inherited risk factor for venous thrombosis:
Answer:
Factor V Leiden gene mutation is the most common inherited cause of an increased risk of venous thrombosis. Activated protein C normally breaks down activated factor V and so should slow the clotting reaction and prolong the APTT, but a mutation in the factor V gene makes factor V less susceptible to cleavage by activated protein C, resulting in increased levels of activated factor V.Venous Thrombosis
Pathology / Haematology / Coagulation Disorders
Last Updated: 25th June 2019
There are three main components important in venous thrombus formation described by Virchow's triad:
- Decreased rate of blood flow (e.g. by venous insufficiency, prolonged immobility or varicose veins)
- Hypercoagulability of blood (e.g. by hyperviscosity or thrombophilia disorders)
- Vessel wall damage (e.g. by sepsis, indwelling venous catheter or by previous thrombosis)
Risk Factors for Venous Thrombosis
- Inherited risk factors:
- Factor V Leiden (most common)
- Prothrombin variant
- Protein C or protein S deficiency
- Antithrombin deficiency
- Acquired risk factors include:
- Lupus anticoagulant
- Oestrogen therapy (OCP and HRT)
- Heparin-induced thrombocytopaenia
- Pregnancy and puerperium
- Surgery (especially abdominal, hip and knee surgery)
- Major trauma
- Malignancy (especially of the ovary, brain and pancreas)
- Myeloproliferative disorders
- Acutely ill hospitalised medical patients
- Hyperviscosity, polycythaemia
- Stroke
- Pelvic obstruction
- Nephrotic syndrome
- Dehydration
- Varicose veins
- Previous venous thrombosis
- Age
- Obesity
- Paroxysmal nocturnal haemoglobinuria
- Behcet's disease
Approximately one-third of patients who suffer DVT or PE have an identifiable heritable risk factor, although additional risk factors are usually present when they develop the thrombosis. The history of a spontaneous DVT in a close relative increases an individual's risk of DVT even if no known genetic predisposition can be identified.
Factor V Leiden
Factor V Leiden gene mutation is the most common inherited cause of an increased risk of venous thrombosis. Activated protein C normally breaks down activated factor V and so should slow the clotting reaction and prolong the APTT, but a mutation in the factor V gene makes factor V less susceptible to cleavage by activated protein C, resulting in increased levels of activated factor V.
Heterozygotes for factor V Leiden are at an approximately five- to eight- fold increased risk of venous thrombosis compared to the general population (but only 10% of carriers will develop thrombosis in their lifetime). Homozygotes have a 30 - 140-fold increased risk. The incidence of factor V Leiden in patients with venous thrombosis is approximately 20 - 40%. It does not increase the risk of arterial thrombosis.
Diagnosis of Venous Thrombosis
Deep Vein Thrombosis (DVT):
- Clinical Suspicion
- DVT is suspected in patients with a painful swollen limb
- Signs may include unilateral thigh or calf swelling or tenderness, changes to skin colour, and venous distension
- Plasma D-dimer concentration
- The concentration of fibrin degradation products (FDPs) is raised when there is a fresh thrombosis; this may be used to exclude diagnosis when used in conjunction with a clinical probability tool
- Compression ultrasound
- This is a reliable and practical method for patients with suspected DVT in the legs and other sites
Pulmonary Embolism (PE):
- Clinical Suspicion
- PE is suspected in patients with shortness of breath and pleuritic chest pain
- Signs may include tachycardia, tachypnoea, hypoxia and pyrexia
- Chest x-ray
- This is often normal but may show evidence of pulmonary infarction or pleural effusion
- Electrocardiogram
- This may show right heart strain in severe cases
- Plasma D-dimer concentration
- This may be used to exclude diagnosis when used in conjunction with a clinical probability tool
- Ventilation perfusion (VQ) scintigraphy
- This detects areas of the lungs being ventilated but not perfused
- Computed tomography pulmonary angiography (CTPA)
- Fine slices of the lung are scanned by spiral CT to identify filling defects in the pulmonary arteries
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
