JSM Clinical Case Reports

Cite this article: Meraj F, Sheikh S, Hanif HM (2020) Pancytopenia Resulting from Renal Osteodystrophy as A Consequence of Secondary Hyperparathyroidism. JSM Clin Case Rep 8(2): 1180.

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*Corresponding authorFatima Meraj, Consultant Haematologist, The Indus Hopsital, The Indus Hospital, Plot C-76, Sector 31/5, Opposite Darussalam Society, Korangi Crossing, Karachi-75190, Pakistan, Tel: +92 (21) 35112709-17; E-mail address: fatima.meraj@tih.org.pk

Submitted: 20 October, 2020

Accepted: 26 November, 2020

Published: 28 November, 2020

Copyright © 2020 Meraj F, et al.

ISSN: 2373-9819

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Keywords•Renal osteodystrophy•Osteitisfibrosacystica•End-stage renal disease•Hyperparathyroidism•Howship’s lacunae

Case Report

Pancytopenia Resulting from Renal Osteodystrophy as A Consequence of Secondary HyperparathyroidismFatima Meraj1*, Sumaira Sheikh1, and Hafsa Muhammad Hanif2

1Consultant Haematologist, The Indus Hopsital, Karachi, Pakistan2Resident, Haematology Dept., The Indus Hospital, Karachi, Pakistan

Abstract

Secondary hyperparathyroidism is a known complication of chronic renal disease. Excessive parathyroid hormone induces a form of renal osteodystrophy characterized by bony remodeling (by stimulating osteoblastic and osteoclastic activities) and myelofibrosis. We report the case of a 22-year-old lady with end-stage-renal disease and marked hyperparathyroidism (1140.90pg/ml; reference range: 15-68pg/ml) who developed pancytopenia despite nutritional supplements and weekly erythropoietin injections. Bone marrow examination revealed findings consistent with renal osteodystrophy.

INTRODUCTIONRenal osteodystrophy is a component of the mineral and

bone metabolism disorders that develop as a sequel of CKD (CKD-MBD) [1]. CKD MBD is characterized by abnormalities in calcium, phosphorous, vitamin D and PTH metabolism, abnormalities in bone structure and turnover, and soft tissue calcifications. Renal osteodystrophy is defined as an alteration in bone morphology in patients with CKD.

Renal osteodystrophy is classified into four types as follows:

• Osteitis fibrosa cystica characterized by high bone turnover resulting from increased osteoblastic and osteoclastic activity, as a result of persistent elevation in PTH [1].

• Adynamic bone disease characterized by low bone turnover resulting from decreased osteoblastic and osteoclastic activity, as a result of excessive suppression of PTH production by medication (phosphate binders) [2].

• Osteomalacia characterized by decreased bone mineralization. In the past this was seen as a complication of aluminium based phosphate binders, resulting in aluminium deposition in bone [2]. Since the abandonment of aluminium–based phosphate binders, this complication is now uncommon.

• Mixed uremic osteodystrophy – characterized by high bone turnover and a disproportionate reduction in bone

mineralization, resulting in increased unmineralized osteoid [2].

The definitive diagnosis of renal osteodystrophy and categorization of subtype are done on a “tetracycline-labelled” bone biopsy specimen. However, serum PTH levels can be used as a surrogate indicator of the various subtypes as follows: PTH levels <100 pg/mL are associated with adynamic bone disease, while PTH >450 pg/mL is suggestive of osteitis fibrosa cystica or mixed uremic osteodystrophy [3].

Bone biopsy is the gold standard diagnostic modality. It is indicated in patients in whom determination of the type of renal osteodystrophy will influence management decisions [4]. Examples include [5]:

• Patients with end-stage kidney disease who are planned for parathyroidectomy due to clinical features of hyperparathyroidism but have indeterminate PTH levels (<450pg/ml).

• Patients with chronic kidney disease who have unexplained bone pains or fractures.

• To confirm the diagnosis of adynamic bone disease

A specimen is obtained from the iliac crest after labeling with tetracycline (usually administered for 3 days, 21 days apart). Tetracycline binds to hydroxyapatite in bone and emits fluorescence, allowing the identification of bone. The KDIGO (Kidney Disease: Improving Global Outcomes) working group on renal osteodystrophy has proposed the “TMV” classification

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for reporting bone biopsy specimens [1]. The following three of bone parameters are used: turnover, mineralization and volume. The following table illustrates the differences in these three parameters in the four types of renal osteodystrophy (Table 1).

Osteitis fibrosa cystica (which represents our current clinical case) is histologically characterized by bone marrow fibrosis, with extension of fibrous tissue and osteoclasts into trabeculae. In addition, there is increased bone resorption, manifested by surface excavation (Howship’s lacunae containing osteoclasts). Hemosiderin laden macrophages and foreign body-type giant cells are also seen in increased numbers [6].

CLINICAL PRESENTATIONWe describe the case of a 24 year old female with End Stage

Renal Disease, on haemodialysis since the age of 21 years. She presented with complains of swelling around the site of her arteriovenous fistula on her left arm since 2-3 months. She was on weekly erythropoietin, antihypertensives and nutritional supplements (vitamin B12, folic acid and calcium), despite which she was receiving with fortnightly to monthly red cell concentrates since 2 years. CBC showed normocytic, normochromic anemia (Haemoglobin 5.4g/dl, WBC count 3.98x10^9/L and Platelet count 114x10^9/L). Reticulocyte count was 2.4%, serum B12 was raised (>2000pg/ml) and RBC folate level was within normal limits. Her serum parathyroid hormone level was markedly elevated (1140.90pg/ml; reference range: 15-68pg/ml). Pre-dialysis biochemical tests included raised serum creatinine(9.06mg/dl), normal serum calcium(9.1mg/dl), hyperphosphatemia (5.4mg/dl) and raised alkaline phosphatase (543 U/L). Serum vitamin D was severely deficient (7.2ng/ml). Ultrasound Abdomen showed no visceromegaly, reduced hepatic parenchymal echogenecity, pelvic ascites and bilateral atrophic kidneys. Computed tomography of the chest showed bilateral atelectatic changes in the lungs.

She was transfused several units of red cell concentrates; However, with time she progressed into pancytopenia (Haemoglobin 9.7g/dl, WBC count 2.1x10^9/L and Platelet count 48x10^9/L). Bone marrow aspiration and trephine biopsy were performed to evaluate the cause of pancytopenia.

RESULTSThe bone marrow aspirate was a dry tap with scattered

neutrophils, lymphocytes and few erythroid precursors. However, touch imprints of trephine biopsy showed a cellular specimen exhibiting trilineage haematopoiesis, with normoblastic erythropoiesis, all stages of myeloid maturation and adequate megakaryocytes. Few scattered osteoclasts were also noted.

Haemotoxylin and Eosin stained sections of trephine biopsy showed three cores, comprising of soft tissue, cortex and good length subcortical and medullary marrow. One core showed cellular marrow with trilineage haematopoiesis. The other cores were markedly hypocellular and showed irregular bony trabeculae with prominent fibrous tissue and osteoclasts (Figure 1). Prominent resorption bays (“Howship’s lacunae”), tunneling into trabeculae by fibrous tissue, haemosiderin laden macrophages and increased vascularity were also noted [Figure 2]. Osteoclasts were highlighted by immunohistochemical

staining for TRAP (tartarate-resistant acid phosphatase) [Figure 3], and increased vascularity was highlighted by CD34.

In the involved cores, reticulin stain showed diffuse and dense increase in reticulin with extensive intersections (Grade MF-02) (Figure 4).

Overall clinical and bone marrow findings, along with hyperparathyroidism, are suggestive of renal osteodystrophy secondary to hyperparathyroidism.

DISCUSSIONOur case illustrates an example of marked secondary

hyperparathyroidism, associated with pancytopenia and suboptimal response to erythropointin and hematinics, due to replacement of cellular marrow by fibrous tissue. In these patients, parathyroidectomy has been shown to improve anemia and reduce the requirements for exogenous erythropoietin therapy [7].

Two similar cases have been reported in recent literature. Yeo JH, Islam A reported the case of a 24-year-old female who

Table 1: Types of Renal Osteodystrophy.

Turnover Mineralization VolumeMild hyperparathyroid-

related bone disease Moderate Normal Normal

Osteitis fibrosa cystica High Normal High

Adynamic bone disease Low Normal Low to normal

Osteomalacia Low Abnormal Low to medium

Mixed uremic osteodystrophy High Abnormal Normal

Figure 1 Low power view (x4) showing irregular bony trabeculae and replacement of hematopoietic marrow by fibrous tissue.

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A B

C

Figure 2 Higher power view (x10) showing tunneling into trabeculae by fibrous tissue (Figure A, B; red arrows), irregular bony trabeculae (Figure C) and surface excavation of bony trabeculae (Howships’s lacunae) (Figure C: red arrows).

Figure 3 Immunohistochemistry for TRAP (tartarate-resistant acid phosphatase) highlighting positivity in scattered osteoclasts.

Figure 4 Reticulin stain showing myelofibrosis.

developed worsening pancytopenia while on haemodialysis, despite erythropoietin injections and adequate supplementation of haematinics [8]. A bone marrow biopsy confirmed reticulin grade 4 myelofibrosis. Her cytopenias resolved following parathyroidectomy.

The second case is of a 45 year old male with End-Stage Renal Disease on haemodialysis [9].His blood counts at presentation revealed pancytopenia (white blood cells: 2.3x109/L, haemoglobin: 10.3g/dl, platelets: 85x109/L). His parathyroid hormone level was markedly raised (1786 pg/mL), while serum calcium was 7.2mg/dl (range: 8.5-10.2mg/dl) and serum phosphorous was 4.9mg/dl (range:2.5-4.5mg/dl). Bone marrow examination revealed fibrotic bone with bony remodeling.

Secondary hyperparathyroidism is managed by treating hyperphopatemia, which is a stimulus for PTH production, by dietary phosphate restriction and administration of phosphate

binders [10]. In addition, vitamin D deficiency is treated. Specific treatment options for hyperparathyroidism include calcimimetics, calcitriol, synthetic vitamin D analogs or a combination of these agents. The goal is to maintain PTH level less than 2-9 times the upper limit of the normal range for the PTH assay [11]. Refractory hyperparathyroidism may be managed by parathyroidectomy.

In conclusion, in patients with chronic renal disease with marked persistent elevations of PTH (secondary hyperparathyroidism) osteitis fibrosa cystica can present with cytopenias, which should be considered when evaluating and managing such patients.

REFERENCES1. Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, et al. (2006)

Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69: 1945-1953.

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2. Brandenburg VM, Floege J (2008) Adynamic bone disease—bone and beyond. NDT Plus 1: 135-147.

3. Moe SM (2004) Management of renal osteodystrophy in peritoneal dialysis patients. Perit Dial Int 24: 209.

4. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, et al. (2017) Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. Kidney Int 92:26-36.

5. h t t p s : / / w w w . u p t o d a t e . c o m / c o n t e n t s / b o n e - b i o p s y - a n d -the-diagnosis-of-renal-osteodystrophy?search=renal%20osteodystrophy&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2

6. Bain B, Clark DM, Wilkins BS (2009) Bone Marrow Pathology. Somerset: Wiley.

7. Trunzo JA, McHenry CR, Schulak JA, Wilhelm SM (2008) Effect of

parathyroidectomy on anemia and erythropoietin dosing in end-stage renal disease patients with hyperparathyroidism. Surgery 144: 915-918.

8. Yeo JH, Islam A (2018) Renal Failure and Progressive Pancytopenia. J R Coll Physicians Edinb 48: 318-320.

9. Sharma SP, Siu K (2013) Pancytopenia in Secondary Hyperparathyroidism Due to End-Stage Renal Disease. Am J Med 126: e11-12.

10. National Kidney Foundation (2003) K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42: S1.

11. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, et al. (2017) Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. Kidney Int 92: 26-36.

Meraj F, Sheikh S, Hanif HM (2020) Pancytopenia Resulting from Renal Osteodystrophy as A Consequence of Secondary Hyperparathyroidism. JSM Clin Case Rep 8(2): 1180.

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