Rare association of consumptive coagulopathy in visceral leishmaniasis: A case report

Case report

A 28-year-old male patient with febrile pancytopenia (Table 1) associated with coagulopathy, loss of 10 kg in two months, but without other comorbidity, was referred to our haematological service in Recife City, Pernambuco State, Brazil, in February 2019. The causative agent for visceral leishmaniasis (VL) was found in his bone marrow; hepatosplenomegaly was confirmed by abdominal ultrasonography. In addition, serum protein electrophoresis showed a monoclonal peak in the gamma globulin region. After treatment with amphotericin B deoxycholate and liposomal amphotericin B, a review after 13 days’ follow-up, pancytopenia and coagulopathy improved.

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Table 1.

Summary of key laboratory values.

Date	02/13	02/18	02/19	02/21	03/08
Haemoglobin (g/L)	79	69	66	79	95
Haematocrit (%)	26.2	21.5	20.9	25.2	31
Mean corpuscular volume (fl)	79.9	75	76	78.3	90.1
Mean corpuscular haemoglobin (pg)	24.2	24	24	31	27.61
Leucocytes (p/mm 3 )	1310	920	1270	1860	4600
Neutrophils (p/mm 3 )	642 (49%)	460 (50%)	698 (55%)	1169 (62.9%)	1748 (38%)
Platelets (p/mm 3 )	30,000	29,000	33,000	61,000	201,000
Prothrombin time (s)	20	–	–	–	13
International normalised ratio	1.58	1.08	–	0.99	1.02
Partial thromboplastin time (s)	54.2	–	–	–	38
Fibrinogen (g/L)	0.64	–	–	0.92	1.1
D-dimer (ng/dl)	651	–	–	324	299
Lactate dehydrogenase (U/L)	899	–	–	745	–
Ferritin (nmol/L)	–	–	50.8	22.5	–
Anti-HIV-1 and -2 antibody; luetic test; hepatitis B virus S antigen (HBsAg); anti-hepatitis B core antibody (anti-HBc IgM and IgG); anti-HCV antibody	Nonreactive

Discussion

Consumption coagulopathy was confirmed by the ISTH DIC scoring system (score = 7). ¹ This haematological profile demanded a bone marrow aspiration, since the principal differential diagnosis would be acute promyelocytic leukaemia. By this examination, the causative agent for VL was fortuitously detected. ²

Hepatosplenomegaly, along with a monoclonal peak in the gamma globulin region detected in the protidogram, ratifies the diagnosis of VL. Furthermore, the good response to amphotericin B (primarily deoxycholate and later liposomal) supports this conclusion. ³ It is therefore reasonable to infer an association between VL and consumption coagulopathy.

There are several pathophysiological hypotheses to explain such. In VL, there is a blockage of the mononuclear phagocytic system (macrophages are parasitised, and there is gamma interferon deficiency), causing macrophages to produce excess tissue factor. This leads to the activation of the extrinsic pathway and to uncontrolled production of thrombin.

Moreover, there is an increase in the production of interleukin-1 and tumour necrosis factor in the parasitised tissues, contributing to increased tissue factor production. In addition, haemolysis, characteristic of VL, causes the release of adenosine diphosphate from red blood cells and of phospholipoproteins from their membrane, activating the coagulation system. ⁴

In addition, hyperferritinaemia, associated with a persistence of fever and pancytopenia, raises the possibility of secondary HLH, which could occur in the context of VL. Considering that amphotericin B was used, it is worth mentioning that amphotericin B may inhibit several cellular functions of the immune system, including macrophage function, cytokine expression, mitogen and antigen-induced proliferation of T and B cells in vitro as well as the cytolytic function of cytotoxic T cells.

Accordingly, it is reasonable to deduce that, in our case, amphotericin had exerted a dual effect on both HLH and leishmaniasis outcomes. ⁵ Furthermore, cefepime was initiated due to the fever being associated with an absolute number of neutrophils <500/mm³.

Conclusion

In most cases of VL, aspects related to coagulopathy are not well investigated, except for the existence of thrombocytopenia, but more important consequences may lurk hidden.