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Year : 2014  |  Volume : 57  |  Issue : 3  |  Page : 476-479
Spurious platelet count due to cryoglobulins in a patient with smoldering myeloma

1 Department of Pathology, Hemato-Oncology and Bone Marrow (Stem cell) Transplant Unit, India
2 Department of Clinical Hematology, Hemato-Oncology and Bone Marrow (Stem cell) Transplant Unit, India
3 Department of Biochemistry, Christian Medical College & Hospital, Ludhiana, Punjab, India

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Date of Web Publication14-Aug-2014


Use of automated hematology analyzers for routine blood count reporting has increased the reproducibility and accuracy of test results. However, at times, these instruments may generate spurious test results. Such results can result in inappropriate investigations or treatment decisions in patients. Spuriously normal or high platelet counts carry the risk of under diagnosis of the true thrombocytopenia with adverse clinical implications. We present a patient with smoldering myeloma with spurious platelet count due to cryoglobulins.

Keywords: Automated, cryoglobulins, hematology analyzers, platelet count, spurious

How to cite this article:
Kakkar N, John M J, Mathew A, Chawla R. Spurious platelet count due to cryoglobulins in a patient with smoldering myeloma. Indian J Pathol Microbiol 2014;57:476-9

How to cite this URL:
Kakkar N, John M J, Mathew A, Chawla R. Spurious platelet count due to cryoglobulins in a patient with smoldering myeloma. Indian J Pathol Microbiol [serial online] 2014 [cited 2020 May 29];57:476-9. Available from: http://www.ijpmonline.org/text.asp?2014/57/3/476/138784

   Introduction Top

Increasing use of automated hematology analyzers for routine blood count reporting has increased the reproducibility and accuracy of test results. However, this has also led to the recognition of some clinical states and laboratory variables that may result in spurious test values. Some of these artifacts may be instrument specific. Operators of hematology analyzers must be aware of the possible artifacts that may interfere in analyzer functioning. This can avoid erroneous reporting of test results and possible unnecessary investigations in the patient. [1]

Automated enumeration has increased the reliability of the platelet count. Unlike thrombocytosis, in clinical practice, thrombocytopenia is much more alarming for the patients and clinicians alike due to the risk of bleeding. At times, the platelet count may be may be spuriously normal or high and carries the risk of under diagnosis of true thrombocytopenia, which can have adverse clinical implications. Recognition of such spurious platelet counts is thus important to avoid inappropriate treatment. [2] We present a rare cause of spurious platelet count due to cryoglobulins.

   Case report Top

A 64-year-old gentleman presented with complaints of recurrent episodes of cold urticaria and epistaxis since 10 months. He had been diagnosed to have smoldering myeloma 6 months ago with 30% plasma cells in the bone marrow aspirate smears with no evidence of end organ damage and an M-band quantified as 0.7 g%. Bone marrow trephine biopsy showed lambda restriction suggestive of clonality. No M-band was seen on urine electrophoresis. Free light chain assay showed κ-11.5 mg/l, λ-28.80 mg/l, κ/λ ratio-0.399. Immunofixation electrophoresis showed IgG lambda. Beta2 microglobulin was 5.3 mg/dL. There were no lytic lesions on skeletal survey. The patient had been treated for Hodgkin's Lymphoma (Stage IA) 20 years ago and was in complete remission.

Complete blood count was done on BC 3000 plus, Mindray (Shenzhen, China), a 3-part automated hematology analyzer showed discrepancy between manual and automated platelet counts and also between automated platelet counts on different analyzers on the same sample done within 24 h. The details are shown in [Table 1].
Table 1: The hematological parameters of the patient and the variable platelet counts obtained manually and on different analyzers

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Peripheral blood smear showed amorphous pale purplish material in the background (arrows) [Figure 1]. Cryoglubulinemia was thus suspected, and the possibility of spurious platelet count due to cryoglobulins was considered. The blood sample was centrifuged at 1500 g for 15 min and plasma was separated. The plasma was stored at 4-8°C. A control sample was also kept alongside. The patient's plasma at 24 h showed white gel like precipitate at the bottom of the tube, thus confirming the presence of cryoglobulins [Figure 2].
Figure 1: Shows the purplish globules of precipitated cryoglobulins (arrows) in the peripheral blood smear (Leishman, ×1000)

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Figure 2: Shows precipitated cryoglobulins as whitish gel like material in the patient's plasma aft er 24 h storage at 4-8°C

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Bilateral bone marrow aspiration and trephine biopsy was done which showed plasmacytosis (up to 60%) on the left side and 66% on the right side [Figure 3], Inset]. One-fourths of the plasma cells showed immature morphology with prominent nucleoli and eccentric nuclei. The background of the bone marrow aspirate smears also showed the presence of purplish coarse granular to amorphous material suggestive of cryoglobulins [Figure 3].
Figure 3: Shows bone marrow aspirate smear with precipitated granular cryoglobulins in the background. Inset: Shows increase in plasma cells (MGG, ×1000)

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Serum protein electrophoresis showed a polyclonal peak in the gamma globulin region (arrow) with a mild rise in gamma globulins, which was not discrete (0.9 g/dL). No definite M-band was identified. Immunofixation showed IgG lambda proteins [Figure 4].
Figure 4: (a) Shows serum electrophoresis with a mild polyclonal rise in proteins. No definite M-band seen, (b) immunofixation study showing IgG lambda proteins

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With a diagnosis of smoldering IgG lambda myeloma, the patient was kept under close outpatient follow-up with monitoring of M-band. Although there was an increase in plasma cells in the bone marrow, he did not have any symptoms of myeloma or any end organ damage. Hence, no treatment was initiated. However, in view of cryoglobulinemia, he was evaluated for hepatitis C virus (HCV) infection, which was found to be negative. The patient was on outpatient follow-up when 3 weeks later he presented to the emergency service with acute onset of chest pain, hemoptysis and suffered a cardiac arrest. He expired 14 h after admission due to suspected acute pulmonary embolism.

   Discussion Top

Widespread use of automated hematology analyzers has enhanced the accuracy of test results and significantly reduced the turnaround time of the complete blood count. However, on some occasions, the automated results may be spurious relating to an unusual pathology in the patient or due to changes induced after sampling. [3]

Spurious elevation of platelet count may be seen in patients with extensive burns, extreme microcytosis (as seen in HbH disease, microangiopathic hemolytic anemia, and red cell fragmentation in burns), micro-organisms like bacteria, fungi or yeast, hyperlipidemia, fragments of white blood cell (WBC) cytoplasm in patients with acute leukemia, hairy cell leukemia, and lymphomas or the presence of cryoglobulins. [2] This has the risk of under evaluation or treatment of a true thrombocytopenia as the patient's reported count could be spuriously normal or high.

Cryoglobulins are circulating immunoglobulins that precipitate in cold temperature between 4°C and 37°C. They may be monoclonal, polyclonal or mixed. Type I cryoglobulins consist of monoclonal immunoglobulins usually either IgM or IgG. Type II cryoglobulins have a mixture of monoclonal IgM and polyclonal IgG. Type III cryoglobulins are a mixture of polyclonal IgM and IgG. Types II and III are referred to as mixed cryoglobulinemias because they consist of both IgG and IgM components. [4]

Cryoglobulins may be seen in varied clinical settings and may pose diagnostic challenges when clinically unsuspected. Cryoglobulinemia at times may be the initial feature of a previously unsuspected underlying disease. Cryoglobulins may be seen in patients with autoimmune disorders, lymphoproliferative states, multiple myeloma and chronic infective states, especially HCV infection. However, they may occasionally be seen in patients without any apparent disorder. [4],[5],[6]

The percentage of patients with circulating cryoglobulins who develop symptoms varies from 2% to 50%. The most common presentation, the triad of purpura, arthralgia, and weakness, is reported in 80% of patients at disease onset. [6]

Our patient had presented earlier with cold urticaria. A condition sometimes associated with cryoglobulinemia. However, the occurrence of cryoglobulins on the peripheral blood smear was an incidental finding.

Spurious thrombocytosis as well as leukocytosis have been reported in association with cryoglobulinemia when the counts are performed on automated hematology analyzers. [7],[8],[9],[10]

These spuriously cell counts occur due to the cryoglobulin particles being counted as WBCs or platelets when they approximate their size, structure, and shape as they pass through the aperture of the analyzer. At times, even the histograms generated for white cells and platelets may show characteristic abnormalities. Our patient had smoldering myeloma and cryoglobulins caused a spurious normal platelet count when reported on three different hematology analyzers although the patient actually had thrombocytopenia. This variability is explained on the basis of differential precipitation of cyroglobulins in different instruments depending on the temperature and the in vitro blood-diluent interaction.

A careful peripheral blood smear examination can be helpful in the detection of cryoglobulins, especially when there is a discrepancy between the automated and manual white cell or platelet counts. Cryoglobulins may occasionally be seen in the peripheral blood smears as needle-like, boat-shaped or geometrical extracellular or intracellular material. Extracellular precipitation may take the form of grayish precipitates, fusiform or needle-shaped crystals, basophilic or pinkish globules, or shapeless aggregates. Intracellular cryoglobulin inclusions should be distinguished from other neutrophil inclusions, such as Döhle bodies, abnormal mucopolysaccharides, and red blood cell fragments ingested in hemolytic anemias. [7] In our patient, cryoglobulins were present extracellularly as purplish globules in the peripheral blood smear and as smaller precipitates in the bone marrow aspirate smears.

Advancement in automated hematology analyzers has resulted in falling blood smear review rates across laboratories. However, as more data on spurious results generated by these instruments is becoming available, the importance of the blood smear examination is again being recognized. Awareness of spurious automated results and a review of peripheral blood smear in samples from patients in whom results do not conform to the clinical profile can assist greatly in making the correct diagnosis. A high index of suspicion for the presence of cryoglobulins must be kept when automated blood counts do not match the manual counts or the clinical profile.

   Conclusion Top

A high index of suspicion for the presence of cryoglobulins must be kept in patients with clinical conditions in which these are known to occur especially when the automated platelet count does not conform to the clinical picture or the manual platelet count.

   References Top

Tessier-Marteau A, Geneviève F, Godon A, Macchi L, Zandecki M. Automated hematology analysers and spurious counts. Part 1. Platelets. Ann Biol Clin (Paris) 2010;68:393-407.  Back to cited text no. 1
Bain BJ. Detecting erroneous blood counts. In: Blood Cells: A Practical Guide. 3 rd ed. London: Blackwell Science; 2002. p. 155-74.  Back to cited text no. 2
Zandecki M, Genevieve F, Gerard J, Godon A. Spurious counts and spurious results on haematology analysers: A review. Part I: Platelets. Int J Lab Hematol 2012;29:4-20.  Back to cited text no. 3
Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet 2012;379:348-60.  Back to cited text no. 4
Barnett EV, Bluestone R, Cracchiolo A 3rd, Goldberg LS, Kantor GL, McIntosh RM. Cryoglobulinemia and disease. Ann Intern Med 1970;73:95-107.  Back to cited text no. 5
Trejo O, Ramos-Casals M, García-Carrasco M, Yagüe J, Jiménez S, de la Red G, et al. Cryoglobulinemia: Study of etiologic factors and clinical and immunologic features in 443 patients from a single center. Medicine (Baltimore) 2001;80:252-62.  Back to cited text no. 6
Fohlen-Walter A, Jacob C, Lecompte T, Lesesve JF. Laboratory identification of cryoglobulinemia from automated blood cell counts, fresh blood samples, and blood films. Am J Clin Pathol 2002;117:606-14.  Back to cited text no. 7
Hutchinson CV, Stelfox P, Rees-Unwin KS. Needle-like cryoglobulin crystals presenting as spurious thrombocytosis. Br J Haematol 2006;135:280.  Back to cited text no. 8
Zandecki M, Dupriez B, Fenaux P, Jude B, Watel A, Dracon M, et al. Cytological and ultrastructural assessment of free crystals or precipitates associated with pseudoleukocytosis and pseudothrombocytosis in cryoglobulinemia. Nouv Rev Fr Hematol 1989;31:397-402.  Back to cited text no. 9
Ogawa M, Kabutomori O, Koh T, Futsukaichi Y, Nishiyama M, Fushimi R, et al. Mixed type cryoglobulinemia with discrepancy of platelet counts measured with an automated cell counter and by manual counting method. Rinsho Byori 1991;39:1229-32.  Back to cited text no. 10

Correspondence Address:
Naveen Kakkar
Department of Pathology, Christian Medical College and Hospital, Brown Road, Ludhiana - 141 008, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.138784

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

  [Table 1]

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