Journal of Postgraduate Medicine
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GRAND ROUND CASE
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Year : 2005  |  Volume : 51  |  Issue : 2  |  Page : 137-139  

A case of cranial venous sinus thrombosis and proteinuria

Vikas Agarwal1, S Chauhan2, R Singh2, R Singh2,  
1 Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
2 Department of Medicine, Government Medical College and Hospital, Sector 32, Chandigarh, India

Correspondence Address:
Vikas Agarwal
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow
India




How to cite this article:
Agarwal V, Chauhan S, Singh R, Singh R. A case of cranial venous sinus thrombosis and proteinuria.J Postgrad Med 2005;51:137-139


How to cite this URL:
Agarwal V, Chauhan S, Singh R, Singh R. A case of cranial venous sinus thrombosis and proteinuria. J Postgrad Med [serial online] 2005 [cited 2021 Oct 17 ];51:137-139
Available from: https://www.jpgmonline.com/text.asp?2005/51/2/137/16383


Full Text

An 18-year-old male, presented with history of dyspnoea on exertion, intermittent icterus, colicky abdominal pain, and cola-colored urine (of 6 months duration). There was no history of fever, bleeding, intake of drugs or exposure to radiation. Past history and family history were non-contributory. Examination showed heart rate of 110/minute, respiratory rate of 22/minute, blood pressure of 120/80 mm of Hg, severe pallor and icterus. There was absence of lymphadenopathy, hepato-splenomegaly, skin purpura or bone tenderness.

 Q. What is the most likely diagnosis?



Answer: The clinical presentation is suggestive of intravascular haemolysis. Various causes of intravascular haemolysis include:

1) enzyme deficiencies in the red blood cells (RBC); Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, pyruvate kinase deficiency, and glutathione deficiency,

2) defect in the microvasculature leading to microangiopathic haemolytic anaemia (MHA); prosthetic valve, arterio-venous anastomosis, disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), haemolytic uraemic syndrome (HUS),

3) complement activating antibodies; paroxysmal cold haemoglobinuria (PCH) and

4) acquired defect on the RBC membrane; paroxysmal nocturnal haemoglobinuria (PNH).

Rarely, severe extravascular haemolysis, either due to haemoglobinopathies or warm antibody-mediated phenomenon may give rise to similar clinical manifestations. In view of the age of the patient, episodic nature and duration of six months, G6PD deficiency, microangiopathic haemolysis, PNH and PCH seem to be the more likely possibilities.

 Q. Which laboratory investigations will you ask for?



Answer: Haemoglobin concentration, reticulocyte count, peripheral blood picture, RBC indices, total leukocyte and platelet counts will reflect the degree and type of anaemia and whether the defect is mono-, bi-, or tri-lineage whereas serum bilirubin (direct and indirect), plasma haemoglobin and haptoglobin, urine haemosiderin or haemoglobin will confirm intravascular haemolysis.

Laboratory investigations showed haemoglobin 7.3 gm/dl, total leukocyte count 4200/mm3 (neutrophils 70%, lymphocytes 26%, monocytes 2% and eosinophils 2%), platelet count 60,000/mm3, corrected reticulocyte count of 10%, mean corpuscular volume of 110 fl, mean corpuscular haemoglobin of 35 pg, mean corpuscular haemoglobin concentration of 32 g/dl, macrocytes on peripheral film, and unconjugated hyperbilirubinemia (total 3.2 mg/dl, direct 1.0 mg/dl) with normal aspartate and alanine transaminase and alkaline phosphatase enzymes. Plasma haemoglobin was 30 mg/dl (normal et al failed to list PNH among the possible causes of CVT.[12] Benign intracranial hypertension may present similarly.

Investigation revealed bilateral infarcts in the parieto-occipital region on non-contrast computerized tomogram. Magnetic resonance imaging showed the infarcts [Figure 1]along with bilateral transverse and left sigmoid sinus thrombosis. Urine microscopy showed albumin 3+ without any cells or casts. Twenty-four hour urine albumin was 3.5 gm. Ultrasound of abdomen and colour Doppler for renal veins were normal.

 Q. What are the mechanisms postulated for thrombosis in PNH?



Answer: The proposed mechanisms of thrombosis are: increased platelet activation with platelet microparticle formation and depression of cell surface-mediated fibrinolysis.[13] Increased production of the thrombin during the haemolytic process has been reported to be a predisposing factor for thrombosis. In our case, this being the cause could not be ruled out.

 Q. How common is proteinuria in PNH and what are the other renal manifestations of PNH?



Answer: Proteinuria is extremely uncommon in PNH. Few documented causes include focal segmental glomerular disease,[14] antiglomerular basement disease,[15] and thrombosis of the renal vessels.[16] Kidneys in PNH have been reported to be larger than normal, presumably due to venous congestion and sludging. Marked haemosiderin deposit in the proximal tubule is a common feature. Renal failure has been reported concomitant to pre-existing renal disease or transfusion reactions. Clark et al , in a study evaluating 21 patients of PNH with renal dysfunction, have reported that urinalysis had microscopic haematuria and intermittent proteinuria in addition to haemoglobinuria at some or the other time during the course of the disease. In the same report, cortical infarcts, papillary necrosis, decreased glomerular filtration rate, failure to visualize cortical arterioles and prolonged venous phase on renal angiograms and defect in the concentrating ability have also been reported.[16] Since nephrotic range proteinuria is distinctly uncommon in PNH one should rule out other disorders such as antineutrophilic antibody-associated vasculitis, systemic lupus erythematosus and Goodpasture syndrome.

In our patient, the serology for antinuclear, antineutrophil cytoplasmic and antiglomerular basement antibodies were negative. A renal biopsy revealed deposition of haemosiderin in the tubules without any evidence of glomerular or interstitial pathology.

 Q. What could have been the cause of renal involvement in this patient?



Answer: In this case the exact cause remained unknown. However, since the renal pathology was noticed at the time of CVT and improved with glucocorticoid and anticoagulant therapy, a possibility of microvascular thrombosis[16] being the cause of renal dysfunction cannot be excluded.

 Q. How is PNH treated?



Answer: During acute haemolytic episodes transfusion therapy is helpful in raising the haemoglobin level and suppressing the bone marrow production of RBC. Glucocorticoids and danazol have been reported to reduce the rate of haemolysis. Patients presenting with acute thrombosis require urgent thrombolytic/anticoagulant therapy. Long-term oral anticoagulation therapy is required in cases with cerebral thrombosis or Budd-Chiari syndrome.[4] Bone marrow transplantation should be considered early in the disease course in patients with either bone marrow failure or thrombosis.

 Q. How is response to therapy monitored?



Answer: Response to therapy is monitored by normalization of haemoglobin level, reticulocyte count, platelet count, plasma haemoglobin levels and proteinuria.

Two weeks later his haemogram normalized. Six weeks later urine examination showed albuminuria to be within the normal range [Figure 2]. Computerized tomogram, 11 months later, did not reveal any infarct in the brain or thrombus in the cranial venous sinus. He did not have any more episodes of thrombosis during the past 12 months.

 Q. How common is bone marrow failure in PNH?



Answer: The exact cause of bone marrow failure in PNH is not known. In about 10% of patients, aplastic anaemia evolves and 5% of the known aplastic anaemia patients eventually develop PNH.[2]

 Acknowledgement



The authors are grateful to Professor Neelam Varma, Department of Haematology, Postgraduate Institute of Medical Education and Research, Chandigarh, for carrying out the flowcytometric analysis.

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