Table 3.
CSF, plasma, and serum evidence of altered hemostasis components in multiple sclerosis.
| Hemostasis factors, inhibitors, and receptors | Main findings (patient sample size/methodology) | References |
|---|---|---|
| CSF | ||
| Fibrinogen | Lower levels in CIS vs. PMS (proteomic profile by mass spectrometer in 24 CIS, 16 RRMS, 11 PMS). | (134) |
| TM | Higher levels in OIND vs. SPMS. Ninety percent of TM in CSF is related to intrathecal synthesis (17 relapse, 11 remission, 11 SPMS, 19 OND, 15 OIND). | (135) |
| PLASMA | ||
| FII, FX, Fibrinogen, PC, FII, FX, FXI | Higher FII:c and FX:c in RRMS and SPMS vs. controls. No differences in activity of Fibrinogen, FXI and PC (PT in citrate plasma: 116 RRMS, 10 PPMS, 73 SPMS, 20 controls). | (136) |
| FXII | Higher FXII:c in RRMS and SPMS vs. controls. Higher activity correlates with higher occurrence of relapses and shorter relapse-free period (aPPT in citrate plasma: 138 RRMS, 13 PPMS, 90 SPMS, 19 CIS, 130 controls). | (10) |
| Increased of FXII protein concentration levels and reduced function in MS (aPTT and ELISA on citrate plasma: 12 RRMS, 34 SPMS, 28 PPMS, 49 controls). Intrinsic thrombin generation in 10 PMS, 10 controls. | (137) | |
| FXII, ADAMTS13, HCII, TFPI, TM | Lower ADAMTS13 levels in MS vs. controls. Higher TFPI levels in PMS vs. RRMS and vs. controls. No differences in FXII and HCII (ELISA on plasma EDTA: 85 RRMS, 53 PMS, 42 controls). | (138) |
| FII | Prothrombotic state in RRMS (thrombin generation on citrate plasma: 15 RRMS, 15 PPMS, 19 controls). | (139) |
| Fibrinogen | No differences in fibrinogen levels, PT and aPTT times (42 RRMS and 31 controls). | (140) |
| High levels, particularly associated with active lesions on MRI (17 out 58: 45 CIS, 12 RRMS, 1 PMS). | (141) | |
| vWF, TM | Higher vWF activity in active MS. No differences in TM protein concentration (26 RRMS, 35 controls). | (142) |
| AT | No differences in AT:c (37 RRMS, 32 SPMS, 34 controls). | (143) |
| EPCR | Trend for higher levels in MS (63 MS, 20 controls). | (144) |
| SERUM | ||
| FX, Prothrombin, C1INH, FXIII, Plasminogen | Reduction of FX, prothrombin and C1INH levels in pre- and post-symptomatic MS serum. Reduction in FXIII and plasminogen in post-symptomatic MS (Mass spectrometry (pooled serum of 100 MS vs. pooled serum of 100 controls). | (145) |
| TM | Higher levels in MS during exacerbation vs. remission state, OND, and controls (17 acute relapse, 9 PMS, 13 HAM, 10 non-HAM, 10 OND, 20 controls). | (146) |
| Higher levels in OIND vs SPMS (17 relapse, 11 remission, 11 SPMS, 19 OND, 15 OIND). | (135) | |
| TM, aPC | No differences (100 RRMS, 22 SPMS, 122 controls). | (147) |
| vWF | No difference (9 RRMS, 9 SPMS, 10 PPMS). | (148) |
ADAMTS13, A disintegrin-like and metalloprotease with thrombospondin type 1 motif 13; AT, antithrombin; aPC, activated protein C; aPTT, activated partial thromboplastin time; C1INH, C1 inhibitor; CIS, clinically isolated syndrome; CSF, cerebrospinal fluid; :c, activity; EDTA, ethylenediamine-tetra-acetic acid; ELISA, enzyme-linked immunosorbent assay; EPCR, endothelial protein C receptor; F, factor; FII, thrombin; HAM, HTLV-1-associated myelopathy; HCII, heparin cofactor II; OIND, other inflammatory neurological disorders; OND, other neurological diseases; PC, protein C; PMS, progressive multiple sclerosis; PPMS, Primary Progressive Multiple Sclerosis; PT, prothrombin time; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; TFPI, tissue factor pathway inhibitor; TM, thrombomodulin; vWF, von Willebrand Factor.