The following blood tests are obtained for a newly admitted patient in the ICU, who is intubated and mechanically ventilated.
Parameter | Patient Value | Adult Normal Range | |||||||||||||
FiO2 | 0.5 | ||||||||||||||
pH | 7.17* | 7.35 – 7.45 | |||||||||||||
pO2 | 93 mmHg (12.2 kPa) | ||||||||||||||
pCO2 | 40.0 mmHg (5.2 kPa) | 35.0 – 45.0 (4.6 – 6.0) | |||||||||||||
SpO2 | 95% | ||||||||||||||
Bicarbonate | 14.0 mmol/L* | 22.0 – 26.0 | |||||||||||||
Base Excess | -13.8 mmol/L* | -2.0 – +2.0 | |||||||||||||
Lactate | 1.4 mmol/L | 0.5 – 1.6 | |||||||||||||
Glucose | 7.3 mmol/L* | 3.5 – 6.0 | |||||||||||||
Parameter | Patient Value | Adult Normal Range | |||||||||||||
Sodium | 129 mmol/L* | 135 – 145 | |||||||||||||
Potassium | 5.5 mmol/L* | 3.5 – 5.0 | |||||||||||||
Chloride | 96 mmol/L | 95 – 105 | |||||||||||||
Bicarbonate | 14.0 mmol/L* | 22.0 – 26.0 | |||||||||||||
Urea | 16.3 mmol/L* | 3.0 – 8.0 | |||||||||||||
Creatinine | 659 μmol/L* | 45 – 90 | |||||||||||||
Albumin | 27 g/L* | 35 – 50 | |||||||||||||
Protein | 45 g/L* | 60 – 80 | |||||||||||||
Total bilirubin | 148 μmol/L* | < 26 | |||||||||||||
Aspartate transferase | 1,945 U/L* | < 35 | |||||||||||||
Alanine transferase | 1,218 U/L* | < 35 | |||||||||||||
Alkaline phosphatase | 43 U/L | 30 – 110 | |||||||||||||
g-Glutamyl transferase | 68 U/L* | < 40 | |||||||||||||
Ionised calcium | 0.97 mmol/L* | 1.10 – 1.35 | |||||||||||||
Phosphate | 1.11 mmol/L | 0.80 – 1.50 | |||||||||||||
Ferritin | 181,900 mg/L* | 30 – 400 |
Parameter | Patient Value | Adult Normal Range | |||||||||||||||
Haemoglobin | 132 g/L | 120 – 160 | |||||||||||||||
White Cell Count | 5.2 x 109/L | 4.0 – 11.0 | |||||||||||||||
Platelet count | 24 x 109/L* | 150 – 350 | |||||||||||||||
Parameter | Patient Value | Adult Normal Range | |||||||||||||||
Prothrombin time | 20.0 sec* | 12.0 – 16.5 | |||||||||||||||
INR | 1.8* | 0.9 – 1.3 | |||||||||||||||
APTT | 77.0 sec* | 27.0 – 38.5 | |||||||||||||||
Fibrinogen | 0.7 g/L* | 2.0 – 4.0 | |||||||||||||||
D-Dimer | 66.7 mg/L* | < 0.5 |
a) List the abnormalities. (60% marks)
b) List the most likely diagnosis. (10% marks)
c) List appropriate further investigations, and the initial specific pharmacological treatments of this condition. (30% marks)
Not available.
Let's go through his systematically:
So, there's a triple disorder: a respiratory acidosis, as well as a mixed high and normal anion gap metabolic acidosis. Also:
That's right, this question is a basically unchanged version of Question 24.1, except the stem in 2020 had read, "A previously well 24-year-old male presents with fevers, malaise and jaundice. Microbiological cultures are negative, and despite treatment with broad spectrum antibiotics he continues to deteriorate." This time, the examiners have removed this history from the stem, perhaps because one could make the potent argument that with a ferritin of almost 200,000, there's really nothing else this could be.
b) This is haemophagocytic syndrome, or haemophagocytic lymphohstiocytosis (HLH).
c)
Appropriate further investigations would have to include some additional tests, as what results we have been given do not yet fit the diagnostic criteria for HLH. From Henter et al (2004),
The diagnosis of HLH can be established if Criterion 1 or 2 is fulfilled. 1. A molecular diagnosis consistent with HLH 2. Diagnostic criteria for HLH fulfilled (5 of the 8 criteria below) Fever Splenomegaly Cytopenias (affecting ≥2 of 3 lineages in the peripheral blood) Hemoglobin <90 g/L (hemoglobin <100 g/L in infants <4 wk) Platelets <100 × 109/L Neutrophils <1.0 × 109/L Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides ≥3.0 mmol/L (ie, ≥265 mg/dL) Fibrinogen ≤1.5 g/L Hemophagocytosis in bone marrow or spleen or lymph nodes. No evidence of malignancy. Low or no NK cell activity (according to local laboratory reference) Ferritin ≥500 μg/L sCD25 (ie, soluble IL-2 receptor) ≥2400 U/mL
So, we don't have a molecular diagnosis, and zero history (so we can't confirm fever or splenomegaly). We do have low platelets, low fibrinogen, and raised ferritin. We need a few more criteria to be satisfied. Thus, the tests we need to send are as follows:
Initial specific pharmacological treatments, from La Rosée et al (2019):
Henter, Jan‐Inge, et al. "HLH‐2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis." Pediatric blood & cancer 48.2 (2007): 124-131.
La Rosée, Paul, et al. "Recommendations for the management of hemophagocytic lymphohistiocytosis in adults." Blood, The Journal of the American Society of Hematology 133.23 (2019): 2465-2477.