Pathology
Haematology
Which of the following laboratory findings is NOT typical of disseminated intravascular coagulation (DIC):
Answer:
Typical Laboratory Findings in DIC:- Low platelet count
- Low fibrinogen concentration
- Prolonged PT
- Prolonged TT
- Prolonged APTT
- High levels of FDPs (e.g. D-dimers)
- Features of haemolysis
Acquired Coagulation Disorders
Pathology / Haematology / Coagulation Disorders
Last Updated: 25th June 2019
The acquired coagulation disorders are more common than the inherited disorders. Unlike the inherited disorders, multiple clotting factor deficiencies are usual.
Acquired coagulation disorders:
- Deficiency of vitamin K-dependent factors
- Haemorrhagic disease of the newborn
- Biliary obstruction
- Malabsorption of vitamin K
- Vitamin K antagonist therapy (e.g. warfarin)
- Liver disease
- Disseminated intravascular coagulation (DIC)
- Inhibition of coagulation
- Specific inhibitors e.g. antibodies against factor VIII
- Non-specific inhibitors e.g. antibodies found in SLE
- Miscellaneous
- Diseases with M protein production
- L-Asparaginase
- Therapy with heparin, defibrinating agents or thrombolytics
- Massive transfusion syndrome
Vitamin K deficiency
Fat-soluble vitamin K is obtained from green vegetables and bacterial synthesis in the gut. Deficiency may present in the newborn (haemorrhagic disease of the newborn) or in later life.
Deficiency may be caused by an inadequate diet, malabsorption or inhibition of vitamin K by drugs such as warfarin. The activity of factors II, VII, IX and X are vitamin K dependent as well as that of protein C and protein S. Both PT and APTT are prolonged.
Liver Disease
Multiple haemostatic abnormalities in liver disease contribute to a bleeding tendency and may exacerbate haemorrhage from oesophageal varices:
- Biliary obstruction impairs absorption of vitamin K and thus synthesis of factors II, VII, IX and X
- Severe hepatocellular disease often results in reduced levels of factor V and fibrinogen and increased amounts of plasminogen activator
- Decreased thrombopoietin production from the liver contributes to thrombocytopaenia
- Functional abnormality of fibrinogen is found in many patients
- Hypersplenism associated with portal hypertension results in splenic sequestration of platelets and thrombocytopaenia
- DIC may occur
- The net haemostatic imbalance in liver disease may be prothrombotic or haemorrhagic
Disseminated Intravascular Coagulation
Pathogenesis:
DIC is characterised by a widespread inappropriate intravascular deposition of fibrin with consumption of coagulation factors and platelets. This may occur as a consequence of many disorders that release procoagulant material into the circulation or cause widespread endothelial damage or platelet aggregation. Increased activity of thrombin in the circulation overwhelms its normal rate of removal by natural anticoagulants. In addition to causing increased deposition of fibrin in the microcirculation and widespread platelet aggregation to the vessels, intravascular thrombin formation interferes with fibrin polymerisation. Intense fibrinolysis is stimulated by thrombi on vascular walls and the release of fibrin degradation products again interferes with fibrin polymerisation. The combined action of thrombin and plasmin causes depletion of fibrinogen and all coagulation factors, compounded by thrombocytopaenia caused by platelet consumption.
Causes:
- Infection
- Gram-negative and meningococcal septicaemia, falciparum malaria
- Malignancy
- Leukaemia, Adenocarcinoma
- Obstetric complications
- Amniotic fluid embolism, premature separation of placenta, eclampsia, retained placenta
- Hypersensitivity reactions
- Anaphylaxis, incompatible blood transfusion
- Widespread tissue damage
- Surgery, trauma, burns
- Vascular abnormalities
- Leaking prosthetic valves, cardiac bypass surgery, vascular aneurysms
- Miscellaneous
- Liver failure, pancreatitis, snake bites, hypothermia, heat stroke, acute hypoxia, massive blood loss
Clinical Features:
These are usually dominated by bleeding, particularly from venepuncture sites or wounds. There may be generalised bleeding in the gastrointestinal tract, the oropharynx, into the lungs, the urogenital tract and from the vagina in obstetric cases. Less frequently, microthrombi may cause skin lesions, renal failure, gangrene of the fingers or toes, or cerebral ischaemia.
Laboratory Findings:
- Low platelet count
- Low fibrinogen concentration
- Prolonged PT
- Prolonged TT
- Prolonged APTT
- High levels of FDPs (e.g. D-dimers)
- Features of haemolysis
Management:
The mainstay of treatment for DIC is management of the underlying cause but supportive blood product replacement is often required to prevent haemorrhagic complications. Thrombotic complications may require special products, such as activated protein C.
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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 |
