Fatal thrombotic microangiopathy after a single dose of gemcitabine as fourth-line palliative treatment for metastasized ductal breast carcinoma

Figures & data

Figure 1. Microscopic image of the kidney with microthrombi in capillaries of a glomerulus. Haematoxylin and eosin stain (200 × magnification).

Figure 2. Macroscopy of the central nervous system with hemorrhages. (a) Dorsal view of the cerebrum and cerebellum with multiple, petechial and somewhat larger, partly confluent hemorrhages in cerebral cortex of occipital lobes. (b) Cerebellar hemispheres on cut surface with multiple, petechial and somewhat larger, partly confluent hemorrhages.

Table I. Laboratory examination of the patient.

	Day −3	Day +11	Reference
Hemoglobin	7.9 mmol/1 (12.73 g/dL)	7.7 mmol/1 (12.41 g/dL)	7.3–9.7 mmol/1 (11.76–15.63 g/dL)
Thrombocytes	334 × 10^9/l	202 × 10^9/1	120–350 × 10^9/l
Calcium	3.68 mmol/1 (14.72 mg/dl)	3.88 mmol/1 (15.52 mg/dl)	2.20–2.65 mmol/ (8.8–10.6 mg/dl)
Bilirubin total	14 μmol/l	42 μmol/l	<17 μmol/l
Bilirubin direct	5 μmol/l	19 μmol/l	<5 μmol/l
Alkaline phosphatase	417 U/l	562 U/l	<120 U/l
Gamma glutamyl transferase (GGT)	1 206 U/l	1 481 U/l	<35 U/l
Aspartate aminotransferase (AST)	148 U/l	195 U/l	<40 U/l
Alanine aminotransferase (ALT)	56 U/l	187 U/l	<45 U/l
Lactate dehydrogenase (LDH)	774 U/l	746 U/l	<450 U/l
Urea (BUN)	4.9 mmol/1	6.3 mmol/1	2.5–7.0 mmol/1
Creatinine	78 μmol/l (1.02 mg/dl)	89 μmol/l (1.17 mg/dl)	45–90 μmol/l (0.59–1.18 mg/dl)
Reticulocytes		45‰	<20‰
Haptoglobin		<0.08 g/L	0.30–1.60 g/L
Direct antiglobulin test		negative
D-dimer		4 510 ng/ml	<500 ng/ml
Fibrinogen		5.22 g/1	1.6–3.2 g/1
Peripheral blood smear		Schistocytes and fragmented RBCs
Liquor		Minimal lymphocytosis, no malignant cells

Table II. Incidence of gemcitabine-associated TMA in different studies.

Study	Type tumor	Patients included	Patients TMA	Incidence
Casper et al.	pancreatic carcinoma	44	1 HUS
Fung et al.	non-small cell lung carcinoma, pancreatic carcinoma, gastric carcinoma and biliary carcinoma	78 800	12 HUS	0.015%
Humphreys et al.	pancreatic tumors, sarcoma, breast carcinoma, lymphoma, hepatocellular carcinoma and pseudomyxoma peritonei	2 586	8 TMA	0.31%
Izzedine et al.	breast carcinoma, pulmonary adenocarcinoma and ovarian carcinoma	706	3 TMA	0.4%
Müller et al.	T-cell lymphoma, B-cell lymphoma, adenocarcinoma of bile duct and adenocarcinoma of gallbladder	291	4 HUS	1.4%
Arnadottir et al.	bladder carcinoma, esophagus carcinoma, carcinoma of unknown primary	244	3 TMA	1.4%