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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2021  |  Volume : 32  |  Issue : 2  |  Page : 543-547
Thrombotic microangiopathy with pulmonary hemorrhage: A rare case report

1 Department of Nephrology, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
2 Department of Pathology, JSS Academy of Higher Education and Research, Mysore, Karnataka, India

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Date of Web Publication11-Jan-2022


Thrombotic microangiopathy (TMA) includes various diseases with different etiologies which ultimately results in endothelial damage to the small vasculature leading to thrombosis in the micro vessels, this causes mechanical hemolysis, thrombocytopenia due to platelet consumption and ischemic organ damage. Untreated cases carry high mortality, so identifying the cause for TMA assumes importance. We report a 47-year old hypertensive lady presenting with accelerated hypertension (HTN) and TMA picture with rapidly progressive renal failure. She underwent hemodialysis followed by renal biopsy. Biopsy showed patchy cortical necrosis with hypertensive changes. The patient remained dialysis dependent and succumbed to pulmonary edema and alveolar hemorrhage three weeks after initial diagnosis. TMA in this patient could be due to malignant HTN or atypical hemolytic-uremic syndrome, and finding the exact cause is many times difficult. TMA is a medical emergency; a high index of suspicion is needed especially when there is multisystem involvement on background hemolysis and thrombocytopenia. Finding out the cause for TMA is important for prompt initiation of treatment.

How to cite this article:
Shetty M, Chetan CS, Suchitha S, Prasad S, Krishnamurthy K, Chandrashekar M. Thrombotic microangiopathy with pulmonary hemorrhage: A rare case report. Saudi J Kidney Dis Transpl 2021;32:543-7

How to cite this URL:
Shetty M, Chetan CS, Suchitha S, Prasad S, Krishnamurthy K, Chandrashekar M. Thrombotic microangiopathy with pulmonary hemorrhage: A rare case report. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Jan 26];32:543-7. Available from: https://www.sjkdt.org/text.asp?2021/32/2/543/335468

   Introduction Top

Thrombotic microangiopathy (TMA) includes a heterogeneous group of diseases which have in common an occlusive microvascular pathology characterized by intraluminal platelet fibrin thrombi leading to mechanical hemolysis as the red cells pass through and platelet consumption. It presents clinically as hemolytic anemia, thrombocytopenia, and organ/ tissue injury.[1] The term TMA is commonly described in a setting of hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) although it can complicate various medical conditions[2] as in [Table 1].
Table 1: Etiological classification of thrombotic microangiopathy.

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Any organ or tissue can be affected but more commonly the kidneys because the glomerular microcirculation is vulnerable to endothelial damage and thrombus formation.[1] Early recognition is important to prevent CKD and ESRD. To give a brief insight into the pathogenesis of the different causes of TMA - TTP is caused by severe ADAMTS13 deficiency to less than 10% of normal enzyme activity, typical HUS by Shiga toxin-producing E. coli and atypical HUS due to complement dysregulation.[1] The complement system is always in a state of low-level activation. The C3b generated will get deposited on the pathogens and some on the host tissues. This helps in clearing the pathogens but has the propensity to damage the host tissues. The host tissues including vascular endothelium are normally protected by complement inhibitors which are present at the tissue level and also in the fluid phase. Endothelial damage occurs if there is a breach in these regulatory mechanisms due to either inherited or acquired causes.[3] To differentiate between the various causes of TMA is difficult on clinical grounds and many a times not possible even after extensive laboratory work-up. We present a case of middle-aged hypertensive female patient admitted with accelerated hypertension (HTN), rapidly worsening renal failure and thrombotic microangiopathic clinical picture.

   Case Report Top

A 47-year-old female presented with one-week history of headache and three days history of swelling of both legs and puffiness of the face, she had consulted her general practitioner and recorded to have severe HTN [blood pressure (BP) 220/100 mm Hg]. She was previously diagnosed as hypertensive and had been on telmisartan 40 mg + thiazide 12.5 mg per day for the past two years. In view of her new-onset symptoms, accelerated HTN, and mild renal failure (creatinine 1.7 mg/dL, estimated glomerular filtration rate 35.5 mL) she was referred to higher center for further evaluation. In the emergency ward, she threw one episode of generalized tonic clonic convulsion with BP 220/100. Magnetic resonance imagingscan of the brain showed features of posterior reversible encephalopathy syndrome. BP was controlled with IV antihypertensives and patient managed in the intensive care unit. On further questioning patient reports having noticed thinning of hair and mild darkening of her skin color for the past one to two years. Some of the investigations are presented in [Table 2], other tests include urine routine albumin 2+, RBC 4–5/HPF, pus cells 5–6/HPF, serum LDH 1200 U/L which decreased to 889 U/L, total bilirubin 1.5, direct bilirubin 0.43 mg/dL, Coombs test negative, ANA positive (2+ speckled), peripheral smear showed schistocytes, serum complements normal, ANCA-negative, APLA workup negative, complete ANA profile done later was negative, serology negative for HIV, HBsAg, anti HCV. Ultrasound showed normal renal morphology and renal Doppler - no evidence of renal artery stenosis. 2D ECHO- Normal LV function, no LVH.
Table 2: Chronological assessment of the disease over the days.

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In view of rapidly worsening renal failure, oliguria, fluid overload state patient was initiated on hemodialysis on day 7. Urine showed active sediments and ANA serology being positive she was pulsed with methylprednisolone 500 mg for three days. There was a drop in hemoglobin and platelets necessitating blood transfusions. She underwent renal biopsy by the end of 2nd week. Two cores were taken, it was an adequate specimen. It showed patchy coagulative necrosis, the viable glome-ruli showed wrinkling of the basement membrane with endothelial swelling, one artery showed fibrinoid necrosis, intimal fibroplasia, tunica media hyperplasia, and hyaline arteriosclerosis, one arteriole showed intra-luminal thrombosis [Figure 1],[Figure 2],[Figure 3]. Immunofluorescence was negative for the routine panel. Our patient with malignant HTN, rapidly worsening renal failure, and a TMA like clinical picture became dialysis dependent, renal biopsy showed patchy cortical necrosis with TMA and hypertensive changes. She was anuric and continued on thrice-weekly dialysis, she had anemia requiring blood transfusion and mild thrombocytopenia, BP was well controlled with three antihypertensives. She presented to the emergency room following hemoptysis, shortness of breath, and fall in hemoglobin, computed tomography scan of the lungs was suggestive of diffuse alveolar hemorrhage [Figure 4]. As the patient s clinical condition worsened despite optimization of blood pressure and volume status, other possibilities like atypical HUS was considered and plasmapheresis advised but patient died before it could be initiated.
Figure 1: Patchy cortical necrosis with ghost glomerulus (PAS, ×100).

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Figure 2: Fibrinoid necrosis of an arteriole with wrinkling of the basement membrane of the glomerulus in the vicinity (PAS, ×100).

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Figure 3: Duplication of the internal elastic lamina (PAS, ×400)

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Figure 4: Diffuse alveolar hemorrhage with sparing of apex

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The authors obtained all appropriate consent forms from the patient’s relatives for the publication of the case report.

   Discussion Top

TMA in the above case could be due to malignant HTN versus atypical HUS. There are reports of atypical HUS presenting with alveolar hemorrhage[4],[5] although this complication of atypical HUS is very rare. The cause of alveolar hemorrhage could be thrombotic occlusion of pulmonary micro-vasculature and alveolar wall necrosis.[6] We did not do a detailed complement factor work-up (other than C3 C4 levels), ADAMTS13 and its inhibitor due to nonavailability of these tests. Malignant HTN-induced TMA can present similarly although a long history of HTN, chronic hypertensive changes in the vessels, thrombocytopenia usually of mild degree, and improvement in the patient condition with better control of BP favors malignant HTN as a possible cause. The mechanism here could be sustained endothelial damage.[7] The renal failure in malignant HTN TMA can be of varying severity and recovery may be prolonged. There are case reports of malignant HTN TMA presenting with alveolar hemorrhage.[8] In some cases the vaso-obliterative changes of malignant HTN are so severe that patchy cortical necrosis can occur.[9] In our patient the renal failure and mild degree of thrombocytopenia persisted despite control of BP with the addition of alveolar hemorrhage, this made us consider other possibilities. TMA is a medical emergency and finding out the cause is essential for appropriate patient management. A complete diagnostic workup may not be possible in many centers and it may be worthwhile to consider plasmapheresis at an earlier stage.

Conflict of interest: None declared.

   References Top

Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol 2018;13:300-17.  Back to cited text no. 1
Masias C, Vasu S, Cataland SR. None of the above: Thrombotic microangiopathy beyond TTP and HUS. Blood 2017;129:2857-63.  Back to cited text no. 2
Kerr H, Richards A. Complement-mediated injury and protection of endothelium: Lessons from atypical haemolytic uraemic syndrome. Immunobiology 2012;217:195-203.  Back to cited text no. 3
Derebail VK, Parikh P, Jennette JC, Kshirsagar AV. A rare cause of the pulmonary-renal syndrome: A case of atypical haemolyticuraemic syndrome complicated by pulmonary haemorrhage. Clin Kidney J 2008;1:417-9.  Back to cited text no. 4
Yousuf S, Junaid N, Adeboye A, et al. A unique cause of pulmonary hemorrhage: A case of atypical hemolytic uremic syndrome in a patient with antiphospholipid antibody syndrome. Chest 2017;152:A889.  Back to cited text no. 5
Hong JY, Jung JY, Kang YA, et al. Delayed hemolytic uremic syndrome presenting as diffuse alveolar hemorrhage. Korean J Crit Care Med 2014;29:43.  Back to cited text no. 6
van Montfrans GA, Honnebier UP, Koopmans RP, van den Born BJ. Microangiopathic hemolysis and renal failure in malignant hypertension. Hypertension 2005;45:246-51.  Back to cited text no. 7
Hida K, Wada J, Odawara M, et al. Malignant hypertension with a rare complication of pulmonary alveolar hemorrhage. Am J Nephrol 2000;20:64-7.  Back to cited text no. 8
Sanerkin NG. Vascular lesions of malignant essential hypertension. J Pathol 1971;103:177-84.  Back to cited text no. 9

Correspondence Address:
Chettipunyam Sounderrajan Chetan
Department of Nephrology, JSS Academy of Higher Education and Research, Mysore, Karnataka
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DOI: 10.4103/1319-2442.335468

PMID: 35017350

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]


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