A Case Report of Pregnancy Complicated with Primary Hemophagocytic Lymphohistiocytosis

Figures & data

Table 1 HLH-2004 Diagnostic Criteria and Patient’s Examination Results

HLH-2004 Diagnostic Criteria	Patient
The diagnosis HLH can be established if one of either 1 or 2 below is fulfilled
A molecular diagnosis consistent with HLH	UNC13D
Diagnostic criteria for HLH fulfilled (5 out of the 8 criteria below)
(A) Initial diagnostic criteria (to be evaluated in all patients with HLH)
Fever (T >38.5°C, last >7 days)	Tmax 40.0°C, last >7 days
Splenomegaly	No splenomegaly
Cytopenias (affecting ≥2 of 3 lineages in the peripheral blood):
Hemoglobin <90 g/L	81 g/L
Platelets <100 × 10^9/L	193 × 10^9/L
Neutrophils <1.0 × 10^9/L	1.35 × 10^9/L
Hypertriglyceridemia and/or hypofibrinogenemia
Fasting triglycerides ≥3.0 mmol/L (ie, ≥265 mg/dL)	4.35 mmol/L
Fibrinogen ≤1.5 g/L	1.41 g/L
Hemophagocytosis in bone marrow or spleen or lymph nodes	Hemophagocytosis in bone marrow
No evidence of malignancy	No evidence of malignancy
(B) New diagnostic criteria
Low or absent NK-cell activity (according to local laboratory reference)	CD3-CD16+CD56+%: 6.62%, CD3-CD16+CD56+Abs: 53/μL, indicating a decrease in NK cell count
Ferritin ≥500 microgram/L	25766.52 ng/mL
Soluble CD25 (ie, soluble IL-2 receptor) ≥2400 U/mL	2170.72 U/mL
The results of NK cell CD107a activation test decreased (New test, supplement of HLH-2004 Diagnostic Criteria)	Degranulation of NK cells is a functional defect

Abbreviations: HLH, hemophagocytic lymphohistiocytosis; T_max, maximum temperature; NK, natural killer.

Table 2 Patient’s Treatment Options and Temperature Changes

Date	Tmax (°C)	Treatment
8.31	39.5	Cefazolin Sodium 2g Bid ivgtt
9.1	40.0	Cefazolin Sodium 2g Bid+ Oseltamivir Phosphate 75mg Bid ivgtt
9.2	38.4	Cefoperazone Sodium and Sulbactam Sodium 2g Q8h ivgtt
9.3–9.4	39.6	Cefoperazone Sodium and Sulbactam Sodium 2g Q8h+ Ornidazole 0.5mg Q12h ivgtt
9.5–9.9	40	Ceftriaxone sodium 4g qd+ moxifloxacin 0.4g qd ivgtt
9.10–9.22	36.8	Dexamethasone 16mg qd intravenous ivgtt
9.23–9.29	36.7	Dexamethasone 8.25mg, Qd, profess to convinced (Discharge)
9.30–10.6	36.6	Dexamethasone 3.75mg, Qd, po
10.7–10.13	36.5	Dexamethasone 1.5mg, Qd, po
10.14–11.3	36.6	Dexamethasone 0.75mg, Qd, po
11.4	36.8	Dexamethasone 0.375mg, Qd, po

Notes: T_max, maximum temperature; Bid, bis in die; ivgtt, intravenous drip; Q8h, quaque 8 hours; Qd, quaque day; po, peros.

Figure 1 NK cell degranulation assay. PBMCs were isolated and co-incubated with a specific proportion of K562 cells for stimulation or incubated with medium alone (control group). Flow cytometry was then performed with anti-CD3 (FITC), anti-CD56 (APC) and anti-CD107a-PE labeled samples. CD3-CD56+NK cells were gated to assess their expression in response to K562 stimulation and non-stimulation by measuring amplitude changes in CD107a (NK-ΔCD107a) surface expression. The reference intervals were defined as <5% being deficient, >5% and <10% being abnormal, and >10% being normal.

Figure 2 Bone marrow examination: active bone marrow hyperplasia, normal granulocyte lines with reactivity changes, elevated red blood cell lines, normal megakaryocyte lines, and observed tissue hemophagocytosis. (A) Bone marrow pathology (HE staining, ×80): bone marrow cells phagocytosis of nucleated red cells (as shown by arrow). (B) Bone marrow cytology (Reye’s staining, ×100 oil mirror): bone marrow cells phagocytosis of granulocytes and nucleated red cells.

Figure 3 Exome sequencing revealed heterozygous mutations in UNC13D gene.

Data Sharing Statement

All supporting documents have been submitted along with the case report.