Malignant Shock

Hambley (2021)

A 48-year-old man is brought into the emergency room (ED) by ambulance after he was found unconscious at home. In the ER, a very pale man is seen with low blood pressure (80 mmHg systolic and 60 mmHg diastolic), a high heart rate (115 beats per minute) and a high respiratory rate (~25 breaths per minute, normal is ~12 per minute). He has no fever at this time, possibly due to paracetamol and ibuprofen use.

During the physical examination, the man vomits and clinically deteriorates significantly. When puncturing an IV and arterial line, it is noted that the puncture site continues to bleed profusely. The first laboratory results are now known;

Parameter	ED	Ref.	Units

Hemoglobin	3.5	8-10.5	mmol/L
MCV	100	83-100	fL
Erythrocytes	1.5	4.4-6	⋅10¹²/L
Thrombocytes	20	150-400	⋅10⁹/L
Leukocytes	48	4-10	⋅10⁹/L

CRP	245	<8	mg/L
Procalcitonin	20	<0.1	ng/mL
Creatinine	400	65-115	µmol/L
AST	190	<35	U/L
ALT	140	<45	U/L

pH	7.2	7.35-7.45
PO2	85	80-100	mmHg
PCO2	15	35-45	mmHg
HCO3	9	22-29	mmol/L
lactate	15	0.7-2.1	mmol/L

PT	22	9-12	sec
PTT	45	24-33	sec
Fibrinogen	1	2-4	g/L
D-dimer	>10	<0.5	mg/L

These results show anemia, thrombopenia and leukocytosis. Because of the greatly elevated CRP and Procalcitonin, bacterial infection is assumed. The blood gas shows metabolic acidosis (low pH with low bicarbonate and high lactate production).

Lactate production results from anaerobic oxidation in the tissues due to insufficient blood flow (shock) and thus insufficient supply of oxygen (hypoxia). One of the ways the body can combat acidosis is to exhale the acidic carbon dioxide through respiration. The patient already does this; he has a greatly increased respiratory rate and a low pCO2. This is called respiratory compensation.

Furthermore, laboratory results show dysregulated coagulation with prolonged PT, PTT, decreased fibrinogen and increased D-dimer. The results are consistent with activation of coagulation (increased D-dimer) and consumption of factors (prolonged PT, PTT and decreased fibrinogen). Combined with the thrombopenia and clinical observation of post-bleeding, diffuse intravascular coagulation is presumed.

To assess diffuse intravascular coagulation (DIC), the DIC score is commonly used; in which abnormalities in platelet count, PT, fibrinogen and D-dimer yield a number of points. A score greater than 5 is appropriate for DIC. This patient had a score of 8. See also ISTH DIC score

Intensive Care

Because the way of breathing in respiratory compensation takes a lot of energy and the patient becomes exhausted, the patient is admitted to the intensive care unit, where he is sedated and intubated. Meanwhile, the results of microscopic differentiation are also available, in which the following picture is seen;

Preparation of patient with schistocyes and highly granulated leukocytes.

Highly granular, atypical leukocytes, some of which have a bilobular nucleus. The cells are referred to as promyelocytes.

Schistocytes are seen in the blood smear, which is consistent with the already established DIC; they are the result of erythrocytes breaking up on clots and fibrin filaments in the circulation. In addition, atypical, highly granulated leukocytes were seen, some of which appear to have a bilobular nucleus. The leukocytes do not have a classical phenotype, but are referred to as promyelocytes due to the strong granulation and bilobular nucleus. The overall proportions of the different leukocytes are as follows;

Parameter	ED	Ref.	Units

Blasts	1	0	⋅10⁹/L
Promyelocytes	46	0	⋅10⁹/L
Myelocytes	2	0	⋅10⁹/L
Metamyelocytes	1.1	0	⋅10⁹/L
Bands	0.5	0-0.1	⋅10⁹/L
Segments	1.7	1.5-6.5	⋅10⁹/L
Eosinophils	0	0-0.4	⋅10⁹/L
Basophils	0	0-0.1	⋅10⁹/L
Lymphocytes	3	1-3.5	⋅10⁹/L
Monocytes	0	0.2-0.9	⋅10⁹/L

Given the increase in precursors of the neutrophil series, there is a "left shift. In principle, this is not uncommon in sepsis, but in this case there is too great an increase in the number of promyelocytes. In addition, blasts are not usually seen in single sepsis. In combination with the atypical appearance, the suspicion for Acute Promyelocyte Leukemia arises. CITO DNA diagnostics shows a t(15;17) translocation, confirming the diagnosis of APL.

Course

Despite ventilation, filling, transfusion and vasopression, the patient's hemodynamics fail to correct. The acidosis and hypoxia persist, causing extensive damage to the patient's organs and the patient dies of septic shock and APL within hours of presentation to the ER. At autopsy, small hemorrhages are seen in many organs, which is appropriate for the increased bleeding tendency associated with APL.

Both sepsis and an APL can give rise to DIS. In sepsis, it is the bacteria that lead to activation of the endothelium and coagulation. In the case of an APL, it is mainly the aberrant promyelocytes that produce, among other things, the procoagulant tissue factor (TF). In addition, they express annexin II, a membrane protein that causes plasmin generation; greatly increased plasmin concentrations then cause clot breakdown. The clotting problem in APL is therefore multifactorial; on the one hand, there is thrombopenia due to the leukemia (bone marrow displacement) and consumption of clotting factors due to clot activation; on the other hand, there is actually increased breakdown of clots, which without therapy leads to life-threatening (internal) bleeding.