Pathology
Haematology
Regarding haemolytic uraemic syndrome (HUS), which of the following statements is CORRECT:
Answer:
Haemolytic uraemic syndrome (HUS) in children has many common features of thrombotic thrombocytopaenic purpura but organ damage is limited to the kidneys and ADAMTS13 levels are normal. There is also usually diarrhoea and epileptic seizures may occur. Many cases are associated with E.coli 0157 infection. It is classically associated with the triad of: microangiopathic haemolytic anaemia, thrombocytopaenia and acute kidney injury (AKI).Platelet Bleeding Disorders
Pathology / Haematology / Coagulation Disorders
Last Updated: 22nd November 2021
Abnormal bleeding associated with thrombocytopaenia or abnormal platelet function is characterised by spontaneous skin purpura, mucosal haemorrhage and prolonged bleeding after trauma.
Thrombocytopaenia
Thrombocytopaenia may occur from:
- Failure of platelet production (most common)
- Selective megakaryocyte depression
- Rare congenital defects
- Drugs, chemicals, viral infections
- Part of general bone marrow failure
- Cytotoxic drugs, radiotherapy
- Aplastic anaemia
- Megaloblastic anaemia
- HIV
- Leukaemia, myelodysplasia, myelofibrosis, myeloma, marrow infiltration
- Selective megakaryocyte depression
- Increased destruction of platelets
- Immune
- Autoimmune, idiopathic, post-transfusional, feto-maternal
- Associated with infections or systemic disease
- Drug-induced (e.g. heparin)
- Disseminated intravascular coagulation (DIC)
- Thrombotic thrombocytopaenic purpura (TTP)
- Immune
- Abnormal distribution of platelets
- Splenomegaly e.g. liver disease
- Dilutional loss
- Massive transfusion of stored blood to bleeding patients
Disorders of platelet function are suspected in patients who show skin and mucosal haemorrhage despite a normal platelet count and normal levels of von Willebrand factor.
Platelet Function Disorders
Disorders of platelet function are suspected in patients who show skin and mucosal haemorrhage despite a normal platelet count and normal levels of von Willebrand factor.
These disorders may be inherited or acquired:
- Inherited platelet disorders
- Glanzmann's disease
- Bernard-Soulier syndrome
- Storage pool diseases
- Acquired platelet disorders
- Antiplatelet drugs
- Aspirin
- Dipyridamole
- Clopidogrel and prasugrel
- Abciximab, eptifibatide and tirofiban
- Hyperglobulinemia (associated with multiple myeloma or Waldenstrom's disease)
- Myeloproliferative and myelodysplastic disorders
- Uraemia
- Antiplatelet drugs
Diagnosis
Patients with suspected platelet or blood vessel abnormalities should initially have a blood count and blood film examination. Bone marrow examination is often needed in thrombocytopaenic patients to determine whether or not there is a failure of platelet production. The marrow may also reveal one of the conditions associated with defective production.
In patients with thrombocytopaenia, normal haemoglobin and white cell counts, a negative drug history, normal or excessive numbers of marrow megakaryocytes, and no other marrow abnormality or splenomegaly, ITP is the usual diagnosis. Screening tests for DIC are also useful, as are tests for underlying disease such as SLE or HIV.
When the blood count, including platelet count and blood film examinations are normal, PFA-100 test is used to detect abnormal platelet function. In most patients with abnormal platelet function demonstrated by the PFA-100 test, the defect is acquired and associated either with systemic disease (e.g. uraemia), or with aspirin therapy. If von Willebrand disease is suspected, assay of VWF and coagulation factor VIII are required.
Immune Thrombocytopaenic Purpura
Immune thrombocytopaenic purpura (ITP) may be divided into chronic and acute forms.
Chronic ITP:
Chronic ITP is a relatively common disorder. The highest incidence is in women aged 15 - 50 years. It is the most common cause of thrombocytopaenia without anaemia or neutropaenia. It is usually idiopathic but it may been seen in association with other conditions.
Platelet autoantibodies (usually IgG) result in the premature removal of platelets from the circulation by macrophages of the reticuloendothelial system. In many causes the antibody is directed against the glycoprotein IIb/IIIa or Ib complex. The normal platelet lifespan of 10 days is reduced to a few hours. Total megakaryocyte mass and platelet turnover are increased to approximately five times normal.
The onset is often insidious with petechial haemorrhage, easy bruising, and menorrhagia and the course of the disease is characteristically relapsing and remitting. Many asymptomatic cases are discovered by routine blood count. Laboratory findings demonstrate: low platelet count, abnormally large platelets on blood film and normal/increased megakaryocytes in bone marrow biopsy.
Acute ITP:
Acute ITP is most common in children. In approximately 75% of cases, the episode follows vaccination or infection such as chicken pox or glandular fever. Most cases are caused by non-specific immune complex attachment to platelets. Acute ITP usually has a very sudden onset and the symptoms usually disappear in less than 6 months (often within a few weeks). It is usually a self-limiting condition and over 80% of children recover without treatment; in 5 - 10% of cases a chronic form of the disease develops.
Thrombotic Thrombocytopaenic Purpura
Thrombotic thrombocytopaenic purpura (TTP) may be congenital or acquired. There is a deficiency of the ADAMTS13 metalloprotease which breaks down von Willebrand factor (VWF) multimers anchored to endothelial cells. Acquired TTP follows the development of an inhibitory IgG autoantibody, the presence of which may be stimulated by infection, autoimmune disease, connective tissue disease, certain drugs, stem cell transplantation or cardiac surgery.
TTP has traditionally been described as a pentad of thrombocytopaenia, microangiopathic haemolytic anaemia, neurological abnormalities, renal failure and fever. The microvascular thrombosis consumes platelets, causes variable degrees of tissue ischaemia and infarction and is responsible for the microangiopathic haemolytic anaemia (cells fragment as they circulate through the partially occluded vessels). Increasing platelet aggregation onto the VWF multimers has the potential to form large occlusive platelet thrombi which have the potential to embolise. Thrombocytopaenia, schistocytes in the blood film and a particularly high LDH are sufficient to suggest the diagnosis.
Haemolytic uraemic syndrome (HUS) in children has many common features but organ damage is limited to the kidneys and ADAMTS13 levels are normal. There is also usually diarrhoea and epileptic seizures may occur. Many cases are associated with E.coli 0157 infection. It is classically associated with the triad of: microangiopathic haemolytic anaemia, thrombocytopaenia and acute kidney injury (AKI).
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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 |
