Cancer-Associated Thrombotic Microangiopathy: Literature Review and Report of Five Cases
Abstract
:1. Introduction
1.1. Background
1.2. Objectives
1.3. Rationale and Knowledge Gap
- -
- Chemotherapy-associated TMA
- -
- Cancer-associated TMA
2. Case Reports
2.1. Case 1
2.1.1. Oncological History
2.1.2. Reasons for Consultation
2.2. Case 2
2.2.1. Oncological History
2.2.2. Reasons for Consultation
2.3. Case 3
2.3.1. Oncological History
2.3.2. Reasons for Consultation
2.4. Case 4
2.4.1. Oncological History
2.4.2. Reasons for Consultation
2.5. Case 5
2.5.1. Oncological History
2.5.2. Reasons for Consultation
3. Discussion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Table | Physiopathology | Causes |
---|---|---|
Hemolytic-uremic syndrome (HUS) | Dysregulation of complement and activation of alternative complement pathway |
|
Thrombotic thrombocytopenic purpura (TTP) | ADAMS 13 deficit |
|
Poorly controlled hypertension | Endothelial damage, intimal proliferation, and release of pro-coagulant substances |
|
Disseminated intravascular coagulation (DIC) | Excessive thrombin production, phospholipid release, and platelet consumption |
|
Type | Causes | Physiopathology | Treatment |
---|---|---|---|
Associated with chemotherapy treatment |
|
| Drug discontinuation Supportive treatment (anti-hypertensives, dialysis, periodic transfusions, corticotherapy) Immunoglobulins Eculizumab (NOT IN INDUCED BY TKIs) Rituximab |
Associated with active cancer |
|
| Support treatment Tumor-type-specific chemotherapy Imatinib (in some cases of pulmonary TMA) |
Associated with hematopoietic progenitor transplantation |
|
| Plasma exchange (low evidence) Eculizumab Narsoplimab (MASP 2 inhibitor) |
ORGAN | Diana | Main Clinic | Clinic Secondary | Specific Analytical Alterations | Other Alterations | Biopsy |
---|---|---|---|---|---|---|
KIDNEY | Glomerular capillaries Glomerulus | Oligoanuria Lower extremity edema Generalized anasarca HTA | Nausea Vomiting Asthenia | Increased creatinine Metabolic acidosis Hyperkalemia Hematuria Proteinuria | Fever Renal fossa pain | Endoluminal thrombi Fibrinoid necrosis Intimal thickening Fibrin thrombi Necrotic endothelial cells C3 tanks Mesangiolysis |
LUNG | Arterioles of the pulmonary vasculature Pulmonary capillaries | Progressive dyspnea Asthenia | Orthopnea Weight loss | None Elevation of proBNP Hypoxemia (advanced stages) | EKG S1Q3T3 Tachypnea Tachycardia V/Q defects | Medial and intima-media hypertrophy Increased alveolar macrophages Fibrinoid necrosis Intimal fibrosis |
GASTROINTESTINAL TRACT | Intestinal microvasculature | Abdominal pain Diarrhea Ascites | Gastrointestinal bleeding (hematemesis, melena, rectorrhagia) | Increased urea Elevated LDH Indirect bilirubin elevation | Tachypnea Hypotension | Loss of glands Intraluminal schistocytes Intraluminal microthrombi Intraluminal fibrin |
CENTRAL NERVOUS SYSTEM | Cerebral microvasculature | Headache Blurred vision Seizures Drowsiness Stupor Hemiparesis Aphasia | Alterations in the visual field Coma | Elevation of LDH CRP elevation | Cerebral edema Ischemic stroke Hemorrhagic stroke PRES Syndrome | Thrombosis in the cerebral microvasculature Intimal hypertrophy in cerebral capillaries (very rare autopsies) |
Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | |
---|---|---|---|---|---|
Gender | Woman | Woman | Woman | Woman | Woman |
Age | 55–60 years old | 75–80 years | 70–75 years | 65–70 years old | 60–65 years |
Cancer type | CLI metastatic breast | Metastatic gastric adenocarcinoma | Metastatic gastric adenocarcinoma | Metastatic gastric adenocarcinoma | Gastric adenocarcinoma |
Date of diagnosis | April 2021 | October 2022 | March 2016 | November 2023 | July 2019 |
PFS | 18 months | 7 months | 66 months | 0 months | 5 months |
Line of treatment (metastatic) | 2L (cisplatin) | 1L (paclitaxel) | 1L (carboplatin-paclitaxel) | 1L (folfox) | 2L (paclitaxel-ramucirumab) |
GFR (CKD-EPI) mL/min/1.73 m2 | 20 | 90 | 89 | 54 | 62 |
Creatinine (mg/dL) | 2.56 | 0.5 | 0.66 | 1.2 | 0.98 |
Sodium (mmol/L) | 137 | 134 | 136 | 130 | 141 |
Potassium (mmol/L) | 5.2 | 4.3 | 4.5 | 2.7 | 4.3 |
ALT (U/L) | 105 | 51 | 18 | 67 | 12 |
AST (U/L) | 82 | 130 | NC | 38 | NC |
GGT (U/L) | 121 | 162 | 54 | 61 | 22 |
Bilirubin (mg/dL) | 2.9 | 1.1 | 3.2 | 2.1 | 1.2 |
Direct bilirubin (mg/dL) | 1.9 | NC | 0.9 | 1.1 | 0.7 |
LDH (U/L) | 455 | 1657 | 2793 | 309 | 435 |
C-reactive protein (mg/dL) | 24.8 | 6.68 | 5.71 | 13.81 | 1.43 |
NT-proBNP (pg/mL) | 172 | NC | 3243 | NC | 9556 |
Troponin T (pg/mL) | 3.2 | NC | NC | NC | 148.4 |
Hemoglobin (g/dL) | 10.9 | 8.9 | 8.8 | 9 | 12 |
Leukocytes (×103/μL) | 1.52 | 2.96 | 4.31 | 3 | 12.06 |
Platelets (×103/μL) | 39 | 24 | 32 | 59 | 274 |
Reticulocytes (%) | 2.4 | 2.4 | 13.5 | 3.5 | NC |
Reticulocytes (×103/μL) | 79 | 81.5 | 396.2 | 98.5 | NC |
Schistocytes in smears | Present. More than 5%. | Present. Less than 5%. | Present. More than 5%. | Present. Less than 5%. | NC |
D-Dimer (mg/L) | 2.5 | 35.1 | 20.3 | NC | 2.2 |
ADAMS-13 activity (normal 40–130–6%) | 75% | NC | 30 | 39 | NC |
TP (ref 7.3–11.8 s) | 11.2 | 13.3 | 10.3 | 7.5 | 11 |
TTPA (ref 23.2–30.4 s) | 37 | 22.4 | 30.3 | 26 | 24 |
Fibrinogen (mg/dL) (ref 130–400) | 103.1 | 116.4 | 234 | 525.5 | 110 |
I.N.R | 1.62 | 1.25 | 1.24 | NC | 1.33 |
Haptoglobin (ref 30–200 mg/dL) | Under 8 | NC | NC | ||
Lactate (mmol/L) | 3.1 | 1.4 | 3.2 | 3.2 | 2.5 |
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Posado-Domínguez, L.; Chamorro, A.-J.; Del Barco-Morillo, E.; Martín-Galache, M.; Bueno-Sacristán, D.; Fonseca-Sánchez, E.; Olivares-Hernández, A. Cancer-Associated Thrombotic Microangiopathy: Literature Review and Report of Five Cases. Life 2024, 14, 865. https://doi.org/10.3390/life14070865
Posado-Domínguez L, Chamorro A-J, Del Barco-Morillo E, Martín-Galache M, Bueno-Sacristán D, Fonseca-Sánchez E, Olivares-Hernández A. Cancer-Associated Thrombotic Microangiopathy: Literature Review and Report of Five Cases. Life. 2024; 14(7):865. https://doi.org/10.3390/life14070865
Chicago/Turabian StylePosado-Domínguez, L., A.-J. Chamorro, E. Del Barco-Morillo, M. Martín-Galache, D. Bueno-Sacristán, E. Fonseca-Sánchez, and A. Olivares-Hernández. 2024. "Cancer-Associated Thrombotic Microangiopathy: Literature Review and Report of Five Cases" Life 14, no. 7: 865. https://doi.org/10.3390/life14070865