MRCP Part II - some useful notes

Prolonged APTT
- Heparin
- Anti-phospholipid syndrome
- Haemophilia
* When Factor VIII level normal, this suggests diagnosis of Haemophilia B (IX deficiency). Bleeding time, thrombin time, and PT will be nomral

4 'Ts' for Anterior Mediastinal Mass
- Thymoma
- Teratoma / Germ Cell Tumour
- Thyroid
- Terrible Lymphoma

Causes of TTP - causes
- Infection (e.g. Gastrointestinal, genitourinary sepsis; rocky mountain spotted fever, anthrax)
- Pregnancy, oral contraceptives
- Drugs related (Clopidogrel, ticlopidine, ciclosporin, tacrolimus, quinine, high-dose chemotherapy) possibly due to antibody formation
- Autoimmune / vasculitis (SLE)
- HIV infection
- Metastatic Cancer
- Recent cardiovascular procedures (Catheterisation, angioplasty, vascular bypass, prosthetic heart valve)
- Severe hypertension (>200 / 120 mmHg)

* Aetiology - due to deficiency of ADAMTS 13, a metalloproteinase found in plasma responsible for cleaving the ultra-high molecular weight forms of von Willebrand factor secreted by endothelial cells, contributing to pathogenic platelet aggregation & adhesion.
* Classical manifestations: thrombocytopenia, purpura microantiopathic haemolytic anaemia, neurological findings (confusion, delirium, seizures, hemiparesis, aphasia, malaise, fatigue), renal failure, fever (variably present). Additionals inclue nausea, vomiting, abdominal pain, hypertension, arthalgias, splenomegaly. Mortality high. Severity estimated by degree of anaemia, thrombocytopenia, and LDH.
In contrast to HUS, HUS tends to have higher platelets, more severe renal failure, and neurological manifestations absent.
* Laboratory features:
- Anaemia-mild to very severe
- Thrombocytopenia - invariably present may be very severe
- Blood film - polychromasia (increased young red cells), nucleated red blood cellls
- Raised serum LDH
- Increased indirect (unconjugated) bilirubin
- Reduced haptoglobin
- COOMBs test negative
- ADAMTS 13 activity decreased
- Proteinuria, microscopic haematuria
- Elevated urea, creatinine.
- PT, APTT, fibrinogen - may be normal or mildly abnormal (If major consumption of clotting factors, diagnosis of TTP doubtful; prolonted APTT suggests circulating anticoagulant - lupus anticoagulant or antiphospholipid syndrome)
- ANA - present in ~20 %
- COmplement, platelet associated IgG usually normal

Normal Reference Values of Blood Count Differentials
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Neutrophils 60%
Lymphocyes 30%
Myelocytes 6%
Eosinophils 3%
Basophils 1%
(60, 30, 6, 3, 1 %)