Table 9.
Vitamin K treatment in VKCFD1 patients with GGCX mutations. This table gives an overview of all patients who received vitamin K treatment for their coagulation factor deficiency and the response to treatment. For each patient, an overview of the PT, aPTT, coagulation factor function (percent of normal activity or in U/dL or U/mL) prior to therapy is given (in italics) and extrahepatic (non-hemostatic) before treatment parameters are shown (in italics), if determined. Further, the clinical response to treatment is mentioned. For P21, P27, P28, and P29, the response to treatment for the ucOC/cOC ratio is given, but the specific vitamin K dose at the time of blood sampling is not mentioned in the original article. Reference values are stated between brackets if they were mentioned in the original article.
| Id | VK R/(age) | PT | INR | aPTT | FII | FVII | FIX | FX | PC | ProS | Extrahepatic Proteins | New Bleeding Episodes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | before treatment | >120 s | - | >180 s | 2 U/dL [77–125 U/dL] | 3 U/dL [63–139 U/dL] | 8 U/dL [63–155 U/dL] | 2 U/dL [55–160 U/dL] | - | - | - | |
| 10 mg sc/week | - | - | - | 18 U/dL [77–125 U/dL] | 25 U/dL [63–139 U/dL] | 37 U/dL [63–155 U/dL] | 15 U/dL [55–160 U/dL] | 45 U/dL [65–146 U/dL] | 34 U/dL [74–126 U/dL] | - | yes | |
| 2 | before treatment | - | - | - | 24 U/dL [77–125 U/dL] | 23 U/dL [63–139 U/dL] | 8 U/dL [63–155 U/dL] | 20 U/dL [55–160 U/dL] | 42 U/dL [65–146 U/dL] | 35 U/dL [74–126 U/dL] | ||
| 10 mg sc/week | - | 2–3.5 | - | 45 U/dL [77–125 U/dL] | 43 U/dL [63–139 U/dL] | 89 U/dL [63–155 U/dL] | 27 U/dL [55–160 U/dL] | 73 U/dL [65–146 U/dL] | 35 U/dL [74–126 U/dL] | - | no | |
| 3 | before treatment | nd * | nd * | nd * | nd * | nd * | nd * | nd * | nd * | nd * | ||
| 10 mg sc/week | - | - | - | 31 U/dL [77–-125 U/dL] | 23 U/dL [63–139 U/dL] | 55 U/dL [63–155 U/dL] | 17 U/dL [55–160 U/dL] | 84 U/dL [65–146 U/dL] | 28 U/dL [74–126 U/dL] | - | no | |
| 4 | before treatment | nd * | nd * | nd * | nd * | nd * | nd * | nd * | nd * | nd * | ||
| 10 mg sc/week | - | - | - | 24 U/dL [77–125 U/dL] | 47 U/dL [63–139 U/dL] | 33 U/dL [63–155 U/dL] | 16 U/dL [55–160 U/dL] | 71 U/dL [65–146 U/dL] | 57 U/dL [74–126 U/dL] | - | no | |
| 5 | before treatment | 49.5 s [11.5 s] | - | 60 s [30 s] | 9% * | 6% * | 7% * | 5% * | - | - | ||
| 10 mg/d IM 2 weeks (VK1) | no effect | - | no effect | - | - | - | - | - | - | - | ? | |
| 7 | before treatment | 11% [70–100%] | - | ratio 1.65 [0.84–1.21] | 26% [50%–150%] | <1% [50%–150%] | 12% [50%–150%] | 13% [50%–150%] | 7% [70%–140%] | 10% [60%–120%] | dp-ucMGP: 2387 pM [35–546 pM] | |
| a. 10 mg/day po 3 months (VK1) | 36% [70–100%] | - | ratio: 1.24 [0.84–1.21] | 46% [50%–150%] | 21% [50%–150%] | 53% [50%–150%] | 27% [50%–150%] | 13% [70%–140%] | 6% [60%–120%] | dp-ucMGP 2750 pM [35–546 pM] | no | |
| b. 20 mg/d po > 1 y † (VK1) | 42% [70–100%] | - | ratio 1.02 [0.84–1.21] | 38% [50%–150%] | 21% [50%–150%] | 54% [50%–150%] | 31% [50%–150%] | 21% [70%–140%] | 8% [60%–120%] | dp-ucMGP 2407 pM [35–546 pM] | no | |
| 10 | before treatment | 21–31 s [11–14 s] | - | - | 20% [65%–150%] | 74–117% [55%–185%] | 48–71% [50%–180%] | 20–22% [65%–185%] | - | - | - | |
| a. 1× parenteral (VK1) | - | normal | - | - | - | - | - | - | - | - | no | |
| b. 10 mg po/d 2 weeks (VK1) | - | - | - | normal | - | normal | normal | - | - | - | no | |
| c. 5 mg/d (VK1) | 14.9 s [12.3–14.6 s] | - | PTT: 25.9 s [27.3–35.3] | - | - | - | - | - | - | - | no | |
| 12 | before treatment | - | 2.76 [0.9–1.14] | ratio 1.44 [0.83–1.18] | 20% [70%–131%] | 34% [69%–134%] | 42% [71%–139%] | 20% [70%–135%] | 47% [65%–132%] | - | - | |
| po | - | 1.94 [0.9–1.14] | ratio: 1.26 [0.83–1.18] | 24% [70%–131%] | 34% [69%–134%] | 54% [71%–139%] | 18% [70%–135%] | 47% [65%–132%] | - | - | no | |
| iv | - | 1.98 [0.9–1.14] | ratio: 1.16 [0.83–1.18] | 20% [70%–131%] | 35% [69%–134%] | 54% [71%–139%] | 18% [70%–135%] | 47% [65%–132%] | 67% [62%–131%] | - | no | |
| 13 | before treatment | - | - | - | 21% * | 42% * | nd * | 36% * | - | - | - | Incidental finding |
| 2 mg/d 6 weeks | - | - | - | 40% | 62% | - | 65% | - | - | ucOC: >9.4 μg/L * | no | |
| 14 | before treatment | >100 s | - | PTT: >100 s | nd * | <1% * | 9% * | 26% * | - | - | - | |
| 5 mg/d po (VK1) | - | - | - | - | - | - | - | - | - | - | ? | |
| 15 | before treatment | 69.8 s [8.4–12.0s] | 7 | 45 s [21–33 s] | 2% [70%–130%] | 3% [65%–140%] | 4% [65%–140%] | <3% [60%–130%] | - | - | - | |
| a. 5 mg/2 days po | 16.1 s [8.4–12.0s] | - | 29 s [21–33 s] | 20% [70%–130%] | 22% [65%–140%] | 46% [65%–140%] | 23% [60%–130%] | 45% [70%–130%] | 9% [65%–130%] | - | no | |
| b. 30 mg/d po | - | - | - | 32% [70%–130%] | 43% [65%–140%] | 58% [65%–140%] | 25% [60%–130%] | - | - | - | no | |
| 21 | before treatment | - | - | - | 35% * | 37% * | 54% * | 13% * | 56% | 37% | ratio ucOC/cOC: 30.3 [1.2] | |
| a. 70 mg (38 y) | - | - | - | 71% | 69% | 90% | 28% | 63% | 48% | ratio ucOC/cOC: 11.9 [1.2] | ? | |
| b. 70 μg (47 y) | - | - | - | 77% | 79% | 84% | 30% | 81% | - | - | ? | |
| c. 105 μg (47 y) | - | - | - | 94% | 76% | 100% | 37% | - | - | - | ? | |
| 22 | before treatment | - | - | - | 30% * | 37% * | 53% * | 29% * | - | - | - | incidental finding |
| a. 6 mg (14 y) | - | - | - | 34% | 53% | 63% | 39% | - | - | - | no | |
| b. 14 mg (20 y) | - | - | - | 41% | 51% | 59% | 26% | 30% | 17% | - | no | |
| c. 70 mg (20 y) | - | - | - | 53% | 59% | 91% | 39% | - | - | - | no | |
| 23 | before treatment | - | - | - | - | 15% (VK R/) * | nd | 6% * | - | - | - | |
| a. 1 × 1 mg (10 days) | - | - | - | - | - | - | 30% | - | - | - | ? | |
| b. 1 × 1 mg (17 days) | - | - | - | - | - | - | 22% | - | - | - | ? | |
| c. 30 mg (7 y) | - | - | - | - | 80% | - | 42% | - | - | - | ? | |
| d. 50 mg (11 y) | - | - | - | 34% | 47% | 40% | 33% | 55% | 27% | - | ? | |
| e. 90 mg (11 y) | - | - | - | 51% | 68% | 54% | 51% | 69% | 35% | - | ? | |
| 24 | before treatment | - | - | - | - | 31% * | - | 20% * | - | - | - | |
| a. 30 mg (10 y) | - | - | - | - | 65% | - | 41% | - | - | - | ? | |
| b. 50 mg (14 y) | - | - | - | 38% | 38% | 46% | 40% | 47% | 25% | - | ? | |
| c. 90 mg (14 y) | - | - | - | 69% | 80% | 67% | 71% | 67% | 38% | - | ? | |
| 25 | before treatment | - | 1.7 * | - | 27% * | 77% * | 56% * | 33% * | - | - | - | |
| a. 1 × 3 mg (1 y) | - | 1.4 | - | 46% | 60% | 61% | 50% | - | - | - | ? | |
| b. 17.5 mg (3 y) | - | 1.3 | - | 61% | 65% | 51% | 67% | - | - | - | ? | |
| 26 | before treatment | - | - | - | - | - | nd * | nd * | - | - | - | |
| a. 140 mg (3 months) | - | - | 174 s | - | - | - | - | - | - | - | ? | |
| b. 21 mg (1 y) | - | 1.6 | - | - | - | 37% | - | - | - | - | ? | |
| c. 23.3 mg (3 y) | - | 2.4 | - | 35% | 40% | 49% | 25% | 27% | 10% | - | ? | |
| d. 23.3 mg (4 y) | - | 1.7 | - | - | - | - | - | - | - | - | ? | |
| 27 | before treatment | - | - | - | - | 54% * | - | 28% * | - | - | ratio ucOC/cOC: 66.9 [1.2] | |
| a. 140 mg (13 y) | - | 1.2 | - | 89% | 108% | 121% | 55% | 53% | 36% | ratio ucOC/cOC: 39.3 [1.2] | ? | |
| b. 140 mg (14 y) | - | 1.1 | - | 87% | 83% | 131% | 53% | 52% | 59% | - | ? | |
| 28 | before treatment | - | - | - | 41% * | 27% * | nd * | 18% * | 76% | - | ratio ucOC/cOC: 4.3 [1.2] | |
| a. 21 mg (12 y) | - | - | - | 62% | 60% | - | 48% | 106% | - | ratio ucOC/cOC: 3.9 [1.2] | ? | |
| b. 21 mg (13 y) | - | - | - | 60% | 67% | 98% | 31% | - | - | - | ? | |
| c. 70 mg (13 y) | - | - | - | 76% | 65% | - | 57% | 99% | - | - | ? | |
| 29 | before treatment | - | - | - | 30% * | 49% * | nd * | 28% * | - | - | ratio ucOC/cOC: 25.8 [1.2] | |
| 70 mg (5 y) | - | - | - | 56% | 75% | 63% | 41% | 30% | 16% | ratio ucOC/cOC: 9.9 [1.2] | ? | |
| 30 | before treatment | 21% | 3.8 * | 41 s [28 s] | 9% * | 35% * | nd * | 30% * | - | - | - | |
| a. 2 × 5 mg/d 3 days | 40% | 2 | 36 s [28 s] | 13% | 69% | 13% | 38% | 38% | - | - | no | |
| b. multiple doses ‡ | no abnormalities at 3.5 y (2 years after cessation treatment) | - | no | |||||||||
| 44 | before treatment | >100 s | - | >150 s | 0.11 U/mL § | 0.12 U/m § | 0.30 U/mL § | 0.09 U/mL § | - | - | - | |
| 2 mg po | - | - | - | good response | modest response | good response | good response | - | - | - | ? | |
| 45 | before treatment | 30 s | - | 38 s | 0.09 U/mL * | 0.21 U/mL * | 0.59 U/mL | 0.17 U/mL * | - | - | - | incidental finding |
| 1 mg iv | - | - | - | good response | good response | no response | no response | - | - | - | ? | |
| 46 | before treatment | >100 s [12.8] | - | - | 3% * | 2% * | - | 3% * | - | - | - | |
| infusion | 14.8 s [12.8 s] | - | - | 72% | 62% | 62% | - | - | - | no | ||
| 47 | before treatment | 98.9 s | 9 * | 53.1s | 2% * | 1.7% * | 4.7% * | 2% * | - | - | ratio ucOC/cOC: 84.5 * | |
| VK1: 5–10 mg/d po or iv (VK1) | 95.4 s ± 11.9 s | 8.9 ± 0.8 | 40.0 s ± 7.3 s | 3.7% ± 0.9% | 3.2% ± 1.7% | 9.1% ± 2.8% | 4.7% ± 2.1% | 4.1% ± 2.1% | 5.6% ± 0.8% | ratio ucOC/cOC: 9.5 * | yes | |
?: not mentioned (in column “new bleeding episodes”); 14 bp del I1: 14 base pair deletion intron 1; (a) PTT: (activated) partial thromboplastin time; d: day (only in column “VK R/”), cOC: gamma-carboxylated osteocalcin; dp-ucMGP: desphospho-uncarboxylated matrix gla protein; FII: coagulation factor II; FVII: coagulation factor VII; FIX: coagulation factor IX; FX: coagulation factor X; Id: identification number; IM: intramuscular; INR: international normalized ratio; nd: not described; VK R/: vitamin K therapy; PC: protein C; po: per os (oral); ProS: protein S; PT: prothrombin time; s: seconds (only in columns “PT and aPTT”); sc: subcutaneous; TMD: transmembrane domain; VK: vitamin K; ucOC: uncarboxylated osteocalcin; y: year (only in column “VK R/”); † therapy also included: +41 mg MK-4/day and 2 mg MK-7/day for 6 months; MK-4 and MK-7 are homologue of vitamin K2; * no reference values in original article or no values, but clearly stated in full-text as deficient; ‡ 2 × 5 mg VK IM/week (2 weeks), then 5 mg VK IM/week (4 weeks), then 5 mg VK IM/month (16 months), then cessation therapy with continued normal coagulation parameters; § deficient factor IX confirmed at 9 years of age.