https://orcid.org/0000-0002-2493-0558
Abstract
Left ventricular assist devices provide circulatory support to heart failure patients while awaiting a suitable donor heart. However, with their increased duration of therapy, complications are seen frequently. Although coagulation disorders (bleeding and thrombosis) are the most common complications, infection is also a major complication associated with significant morbidity. We report a case of a 53-year-old male with a left ventricular assist device who presented with driveline infection. He subsequently developed pancytopenia and was diagnosed with haemophagocytosis. Immediate treatment with intravenous immunoglobulin and methylprednisolone was started. His blood cell count returned to normal levels and the patient became eligible for heart transplantation again. Our case represents the rare occurrence of haemophagocytosis in a patient, which, if unnoticed, could lead to fatal consequences.
INTRODUCTION
Left ventricular assist devices (LVADs) provide circulatory support to patients with heart failure while awaiting a suitable donor heart. However, adverse events are seen frequently.
The MOMENTUM 3 trial comparing centrifugal and axial-flow pumps showed that the most common causes of death during LVAD support were right heart failure, stroke and infection [1].
Haemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening haematological disorder characterized by dysfunctional monocyte activation and haemophagocytosis in the bone marrow. HLH occurs either due to primary immune-system abnormalities or unregulated monocyte activation in response to specific triggers such as infections.
CASE REPORT
A 53-year-old male with a history of dilated cardiomyopathy and LVAD implantation (HeartMate 3, Abbott) 3 years ago, presented at the outpatient clinic with purulent discharge, erythema and heat around the driveline exit area. On admission, his mean blood pressure was 80 mmHg, heart rate was 90 bpm and the tympanic temperature was 37°C. His laboratory tests were standard (Table 1). Wound swab samples were collected before treatment, and empirical antimicrobial therapy was started with intravenous cefepime 2 g 3 times a day. The bacterial culture of the samples returned positive for Pseudomonas aeruginosa. On the ward, he developed a fever of around 39°C. Pancytopenia, elevated triglycerides and hyperferritinaemia were remarkable laboratory results (Table 1).
Patient’s laboratory results on admission and after the diagnosis of HLH
| Parameters | On admission | After HLH | Norms |
|---|---|---|---|
| Lymphocytes (×103/µl) | 5.44 | 1.1 | 0.65–2.8 |
| Monocytes (×103/µl) | 1.14 | 0.53 | 0–0.08 |
| Leucocytes (×103/µl) | 9.44 | 1.65 | 4.5–11.0 |
| Neutrophils (×103/µl) | 5.44 | 0 | 1.51–7.07 |
| Platelets (×103/µl) | 230 | 76 | 150–450 |
| Haemoglobin (g/dl) | 12.5 | 12.3 | 13.1–17.1 |
| C-reactive protein (mg/dl) | 23.3 | 210 | 0–5 |
| Ferritin (µg/dl) | 23 860 | 30–400 | |
| Triglycerides (mg/dl) | 540 | 150 | |
| Total bilirubin (mg/dl) | 0.53 | 0.76 | 0.1–1 |
| Conjugated bilirubin (mg/dl) | 0.09 | 0.34 | <0.25 |
| Uric acid (mg/dl) | 8.6 | 7.9 | 3.5–7.2 |
| Serum glutamic oxaloacetic transaminase (SGOT) (U/l) | 23 | 70 | <35 |
| Serum glutamic pyruvic transaminase (SGPT) (U/l) | 15 | 12 | <45 |
| Parameters | On admission | After HLH | Norms |
|---|---|---|---|
| Lymphocytes (×103/µl) | 5.44 | 1.1 | 0.65–2.8 |
| Monocytes (×103/µl) | 1.14 | 0.53 | 0–0.08 |
| Leucocytes (×103/µl) | 9.44 | 1.65 | 4.5–11.0 |
| Neutrophils (×103/µl) | 5.44 | 0 | 1.51–7.07 |
| Platelets (×103/µl) | 230 | 76 | 150–450 |
| Haemoglobin (g/dl) | 12.5 | 12.3 | 13.1–17.1 |
| C-reactive protein (mg/dl) | 23.3 | 210 | 0–5 |
| Ferritin (µg/dl) | 23 860 | 30–400 | |
| Triglycerides (mg/dl) | 540 | 150 | |
| Total bilirubin (mg/dl) | 0.53 | 0.76 | 0.1–1 |
| Conjugated bilirubin (mg/dl) | 0.09 | 0.34 | <0.25 |
| Uric acid (mg/dl) | 8.6 | 7.9 | 3.5–7.2 |
| Serum glutamic oxaloacetic transaminase (SGOT) (U/l) | 23 | 70 | <35 |
| Serum glutamic pyruvic transaminase (SGPT) (U/l) | 15 | 12 | <45 |
HLH: haemophagocytic lymphohistiocytosis.
Patient’s laboratory results on admission and after the diagnosis of HLH
| Parameters | On admission | After HLH | Norms |
|---|---|---|---|
| Lymphocytes (×103/µl) | 5.44 | 1.1 | 0.65–2.8 |
| Monocytes (×103/µl) | 1.14 | 0.53 | 0–0.08 |
| Leucocytes (×103/µl) | 9.44 | 1.65 | 4.5–11.0 |
| Neutrophils (×103/µl) | 5.44 | 0 | 1.51–7.07 |
| Platelets (×103/µl) | 230 | 76 | 150–450 |
| Haemoglobin (g/dl) | 12.5 | 12.3 | 13.1–17.1 |
| C-reactive protein (mg/dl) | 23.3 | 210 | 0–5 |
| Ferritin (µg/dl) | 23 860 | 30–400 | |
| Triglycerides (mg/dl) | 540 | 150 | |
| Total bilirubin (mg/dl) | 0.53 | 0.76 | 0.1–1 |
| Conjugated bilirubin (mg/dl) | 0.09 | 0.34 | <0.25 |
| Uric acid (mg/dl) | 8.6 | 7.9 | 3.5–7.2 |
| Serum glutamic oxaloacetic transaminase (SGOT) (U/l) | 23 | 70 | <35 |
| Serum glutamic pyruvic transaminase (SGPT) (U/l) | 15 | 12 | <45 |
| Parameters | On admission | After HLH | Norms |
|---|---|---|---|
| Lymphocytes (×103/µl) | 5.44 | 1.1 | 0.65–2.8 |
| Monocytes (×103/µl) | 1.14 | 0.53 | 0–0.08 |
| Leucocytes (×103/µl) | 9.44 | 1.65 | 4.5–11.0 |
| Neutrophils (×103/µl) | 5.44 | 0 | 1.51–7.07 |
| Platelets (×103/µl) | 230 | 76 | 150–450 |
| Haemoglobin (g/dl) | 12.5 | 12.3 | 13.1–17.1 |
| C-reactive protein (mg/dl) | 23.3 | 210 | 0–5 |
| Ferritin (µg/dl) | 23 860 | 30–400 | |
| Triglycerides (mg/dl) | 540 | 150 | |
| Total bilirubin (mg/dl) | 0.53 | 0.76 | 0.1–1 |
| Conjugated bilirubin (mg/dl) | 0.09 | 0.34 | <0.25 |
| Uric acid (mg/dl) | 8.6 | 7.9 | 3.5–7.2 |
| Serum glutamic oxaloacetic transaminase (SGOT) (U/l) | 23 | 70 | <35 |
| Serum glutamic pyruvic transaminase (SGPT) (U/l) | 15 | 12 | <45 |
HLH: haemophagocytic lymphohistiocytosis.
He was admitted to the intensive care unit with a differential diagnosis of sepsis and haemophagocytosis. Cefepime was replaced with intravenous meropenem 1 g 3 times a day. The peripheral blood smear revealed dysplasia in leucocytes; anisocytosis and poikilocytosis in erythrocytes. Bone marrow aspiration was performed and revealed haemophagocytosis (Fig. 1). After the diagnosis, the patient was started on intravenous immunoglobulin (1g/kg/day) for 2 days and methylprednisolone (1 mg/kg/day) for 3 days. Following treatment, his blood parameters returned to normal, and maintenance dose methylprednisolone (1 mg/kg/day) was continued for 2 additional days in order to complete the treatment to 5 days. To date, leucocytes remain stable within normal levels and the patient is considered eligible for heart transplantation again.
Haemophagocytosis.(A) Haemophagocytosis of the erythrocytes by the macrophages. (B) Haemophagocytosis of a single platelet by the macrophage cell.
DISCUSSION
Despite being an effective strategy in advanced heart failure, the incidence of LVAD-related infectious complications remains high.
HLH is a fatal disease with a median survival of 1.8–2.2 months without treatment [2]. Diagnosis is made if at least 5 of the following 8 criteria are fulfilled: fever, splenomegaly, cytopenia, hypertriglyceridaemia/hypofibrinogenaemia, haemophagocytosis, low/absent natural killer cell activity, hyperferritinaemia and elevated soluble CD25 receptor [3]. Our patient satisfied 5 of the criteria.
Cheng et al. [4] reported 4 cases of HLH in LVAD patients who presented early post-implantation with persistent fever. Treatment with steroids and etoposide enabled 3 patients to survive orthotropic heart transplantation.
During LVAD therapy, prolonged exposure to a large body of foreign material results in the form of immune dysregulation, which was described to be mediated by aberrant T-cell activation at the LVAD surface, increased in vivo activation and spontaneous apoptosis of circulating T cells [5]. Another important aspect is the decrease in the release of Th1 but not in Th2 cytokines resulting in B-cell hyperactivity which was proposed to explain the higher rate of allosensitization in LVAD patients [5]. Immune dysregulation inflicted by LVAD therapy could have played an additive role above the more apparent infectious trigger in this case.
In conclusion, we believe that HLH should be considered within the differential diagnosis when prolonged fevers and sudden changes in blood count are present in an LVAD patient, and further investigations should be made promptly.
Conflict of interest: none declared.
