Clinical characteristics, outcomes and complement studies in patients with CAPS
| Pt. No. . | Age/sex . | Presentation . | Definite/Probable CAPS . | Prior APS diagnosis . | Trigger . | aPL profile* . | Repeat aPL profile* (at least 12 wk apart) . | mHam+ . | Mutations† . |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 45/M | Ischemic toe after initiation of ITP therapy, DVT, pulmonary embolism, myocardial infarction, and renal insufficiency | Probable | + | ITP treatment (eltrombopag) | DRVVT+, hexagonal PL+, PNP+, aβ2GP-I IgG 52, aβ2GP-I IgM 34, aCL IgG 126, aCL IgM 24 | DRVVT+, hexagonal PL+, PNP+, aβ2GP-I IgG >150, aβ2GP-I IgM 52, aCL IgG >150, aCL IgM 38 | — | None |
| 2 | 37/F | Subdural hematoma, cardiomyopathy, acute kidney injury, and thrombocytopenia | Probable | + | Myocarditis, possibly viral | DRVVT+, hexagonal PL+, PNP+, aβ2GP-I >150, aβ2GP-I IgM 146, aCL IgG 127, aCL IgM 69 | DRVVT+, hexagonal PL+, PNP+, aβ2GP-I >107, aβ2GP-I IgM >150, aCL IgG 121, aCL IgM 120 | — | None |
| 3 | 40/M | Renal failure (biopsy showed cortical thrombosis and TMA), thrombocytopenia, and pulmonary embolism | Definite | + | Acute appendicitis | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | + | THBD |
| 4 | 67/F | Pulmonary emboli, arterial thrombosis requiring leg amputation (pathology showed widespread small-vessel thrombosis), digital gangrene, and renal failure | Probable | − | Rheumatoid arthritis flare | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | Repeat was not obtained | + | CFHR1- CFHR3, del (homozygous) |
| 5 | 34/F | Renal failure, thrombocytopenia and elevated liver enzymes | Probable | + | Pregnancy | DRVVT+, aCL IgG 131 | DRVVT+, aCL IgG 64 | + | CR1 |
| 6 | 63/M | Thrombocytopenia, renal failure, cardiomyopathy with reduced ejection fraction, adrenal hemorrhage, and skin ulcers. Renal biopsy showed TMA | Definite | + | Pyelonephritis | DRVVT+, aCL IgG <10, aCL IgM 28, aβ2GP-I IgG 31, aβ2GP-I IgM <10 | DRVVT+, aCL IgG <10, aCL IgM 28, aβ2GP-I IgG 41, aβ2GP-I IgM <10 | + | CFHR4, CR1 |
| 7 | 49/F | Arterial thrombosis of lower extremities, renal failure, cardiac ischemia, gangrene of the fingertips, thrombocytopenia, and skin necrosis | Probable | + | None | DRVVT+, aCL IgG 62, aCL IgM 66, aβ2GP-I IgG <10, aβ2GP-I IgM 40 | Not repeated after CAPS episode because patient died. Previous testing (>1 y prior) showed: DRVVT+, aCL IgG 21, aCL IgM 25, aβ2GP-I IgG 31, aβ2GP-I IgM 15 | − | CR1 |
| 8 | 50/M | Hepatic, spleen, and retinal infarction and renal failure | Probable | + | Acute cholecystitis and cholecystectomy | DRVVT+, aCL IgG >100, aCL IgM <10, aβ2GP-I IgG >100, aβ2GP-I IgM 14 | DRVVT+, aCL IgG, >100, aCL IgM <10, aβ2GP-I IgG >100, aβ2GP-I IgM 14 | + | None |
| 9 | 46/F | Diffuse hepatic infarction and evidence of microvascular thrombosis in the lungs, spleen, and possibly the kidneys. Relapsed about 6 mo after initial presentation with recurrent hepatic infarcts. | Probable | − | None | DRVVT+, aCL IgG 143, aCL IgM 73, aβ2GP-I IgG 61 | aCL IgG 52.5 (on plasmapheresis); DRVVT not repeated because of ongoing anticoagulation | + | CFHR1- CFHR3, del (homozygous) |
| 10 | 51/M | Multiple thrombi on mitral valve, renal failure, infarcts and ischemic injury of liver and spleen, and multiple small-vessel strokes | Definite | + | Mitral valve replacement | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | — | None |
| Pt. No. . | Age/sex . | Presentation . | Definite/Probable CAPS . | Prior APS diagnosis . | Trigger . | aPL profile* . | Repeat aPL profile* (at least 12 wk apart) . | mHam+ . | Mutations† . |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 45/M | Ischemic toe after initiation of ITP therapy, DVT, pulmonary embolism, myocardial infarction, and renal insufficiency | Probable | + | ITP treatment (eltrombopag) | DRVVT+, hexagonal PL+, PNP+, aβ2GP-I IgG 52, aβ2GP-I IgM 34, aCL IgG 126, aCL IgM 24 | DRVVT+, hexagonal PL+, PNP+, aβ2GP-I IgG >150, aβ2GP-I IgM 52, aCL IgG >150, aCL IgM 38 | — | None |
| 2 | 37/F | Subdural hematoma, cardiomyopathy, acute kidney injury, and thrombocytopenia | Probable | + | Myocarditis, possibly viral | DRVVT+, hexagonal PL+, PNP+, aβ2GP-I >150, aβ2GP-I IgM 146, aCL IgG 127, aCL IgM 69 | DRVVT+, hexagonal PL+, PNP+, aβ2GP-I >107, aβ2GP-I IgM >150, aCL IgG 121, aCL IgM 120 | — | None |
| 3 | 40/M | Renal failure (biopsy showed cortical thrombosis and TMA), thrombocytopenia, and pulmonary embolism | Definite | + | Acute appendicitis | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | + | THBD |
| 4 | 67/F | Pulmonary emboli, arterial thrombosis requiring leg amputation (pathology showed widespread small-vessel thrombosis), digital gangrene, and renal failure | Probable | − | Rheumatoid arthritis flare | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | Repeat was not obtained | + | CFHR1- CFHR3, del (homozygous) |
| 5 | 34/F | Renal failure, thrombocytopenia and elevated liver enzymes | Probable | + | Pregnancy | DRVVT+, aCL IgG 131 | DRVVT+, aCL IgG 64 | + | CR1 |
| 6 | 63/M | Thrombocytopenia, renal failure, cardiomyopathy with reduced ejection fraction, adrenal hemorrhage, and skin ulcers. Renal biopsy showed TMA | Definite | + | Pyelonephritis | DRVVT+, aCL IgG <10, aCL IgM 28, aβ2GP-I IgG 31, aβ2GP-I IgM <10 | DRVVT+, aCL IgG <10, aCL IgM 28, aβ2GP-I IgG 41, aβ2GP-I IgM <10 | + | CFHR4, CR1 |
| 7 | 49/F | Arterial thrombosis of lower extremities, renal failure, cardiac ischemia, gangrene of the fingertips, thrombocytopenia, and skin necrosis | Probable | + | None | DRVVT+, aCL IgG 62, aCL IgM 66, aβ2GP-I IgG <10, aβ2GP-I IgM 40 | Not repeated after CAPS episode because patient died. Previous testing (>1 y prior) showed: DRVVT+, aCL IgG 21, aCL IgM 25, aβ2GP-I IgG 31, aβ2GP-I IgM 15 | − | CR1 |
| 8 | 50/M | Hepatic, spleen, and retinal infarction and renal failure | Probable | + | Acute cholecystitis and cholecystectomy | DRVVT+, aCL IgG >100, aCL IgM <10, aβ2GP-I IgG >100, aβ2GP-I IgM 14 | DRVVT+, aCL IgG, >100, aCL IgM <10, aβ2GP-I IgG >100, aβ2GP-I IgM 14 | + | None |
| 9 | 46/F | Diffuse hepatic infarction and evidence of microvascular thrombosis in the lungs, spleen, and possibly the kidneys. Relapsed about 6 mo after initial presentation with recurrent hepatic infarcts. | Probable | − | None | DRVVT+, aCL IgG 143, aCL IgM 73, aβ2GP-I IgG 61 | aCL IgG 52.5 (on plasmapheresis); DRVVT not repeated because of ongoing anticoagulation | + | CFHR1- CFHR3, del (homozygous) |
| 10 | 51/M | Multiple thrombi on mitral valve, renal failure, infarcts and ischemic injury of liver and spleen, and multiple small-vessel strokes | Definite | + | Mitral valve replacement | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | DRVVT+, aCL IgG <10, aCL IgM <10, aβ2GP-I IgG <10, aβ2GP-I IgM <10 | — | None |
DRVVT, dilute Russell’s viper venom time; ITP, immune thrombocytopenia; DVT, deep venous thrombosis; hexagonal PL, hexagonal phospholipid; PNP, platelet neutralization procedure.
aCL IgG and IgM are expressed in IgG (GPL) and IgM phospholipid units (MPL), respectively. The threshold for a positive assay is 20 GPL for IgG aCL and 20 MPL for IgM. aβ2GP-I IgG and IgM are expressed in standard IgG units and standard IgM units, respectively. The threshold for a positive assay is 20 standard IgG units for IgG aβ2GP-I and 20 standard IgM units for IgM aβ2GP-I. A positive DRVVT indicates that the DRVVT confirm ratio (DRVVT/ DRVVT with added phospholipid) was >1.5.
Patients underwent targeted sequencing via a custom 15 gene panel. Only rare variants with minor allele frequency <0.005 in the genome aggregation database (gnomAD v2) were included.