39:: Thrombin escaping from a site of vascular injury binds to its receptor thrombomodulin (TM) on the intact cell surface. As a result, thrombin loses its procoagulant properties and instead becomes a potent activator of protein C. Activated protein C (APC) functions as a circulating anticoagulant, which specifically degrades and inactivates the phospholipid-bound factors Va and VIIIa. This effectively down-regulates the coagulation cascade and limits clot formation to sites of vascular injury. T = Thrombin, PC= Protein C, Activated Protein C= APC, PS= Protein S
29:
150:, which is responsible for more than 95% of cases. Other genetic causes include Factor V Cambridge (VThr306) and the factor V HR2 haplotype (A4070G mutation). Acquired forms of APC resistance occur in the presence of elevated Factor VIII concentrations.
1080:
373:
Koster T, Rosendaal FR, De Ronde H, Briët E, Vandenbroucke JP, Bertina RM (December 1993). "Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden
Thrombophilia Study".
931:
Amiral J, Vissac AM, Seghatchian J (December 2017). "Laboratory assessment of
Activated Protein C Resistance/Factor V-Leiden and performance characteristics of a new quantitative assay".
966:
de Visser MC, van
Hylckama Vlieg A, Tans G, Rosing J, Dahm AE, Sandset PM, Rosendaal FR, Bertina RM (July 2005). "Determinants of the APTT- and ETP-based APC sensitivity tests".
703:
Douxfils J, Morimont L, Bouvy C (November 2020). "Oral
Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk".
1142:
1135:
251:
anticoagulation therapy. People with APC resistance and initial DVT are treated with a standard anticoagulant regimen, for instance
1128:
833:
Asscheman H, T'Sjoen G, Lemaire A, Mas M, Meriggiola MC, Mueller A, Kuhn A, Dhejne C, Morel-Journel N, Gooren LJ (September 2014).
1259:
146:
and may lead to a hypercoagulable state. This may be hereditary or acquired. The best known and most common hereditary form is
538:
1762:
835:"Venous thrombo-embolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review"
1434:
1417:
1092:
179:
1496:
1448:
189:
892:"Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people"
1502:
1488:
193:
1476:
1439:
1309:
607:"Effects of non-oral postmenopausal hormone therapy on markers of cardiovascular risk: a systematic review"
70:(APC), which normally helps prevent blood from clotting excessively. This results in an increased risk of
1629:
1205:
151:
1584:
1429:
651:"Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk"
1700:
1271:
1252:
751:"Can We Measure the Individual Prothrombotic or Prohemorrhagic Tendency by Global Coagulation Tests?"
1670:
1413:
1242:
1103:
890:
Toorians AW, Thomassen MC, Zweegman S, Magdeleyns EJ, Tans G, Gooren LJ, Rosing J (December 2003).
1757:
1660:
1453:
236:
66:(an increased tendency of the blood to clot) characterized by a lack of a response to activated
1574:
1549:
1507:
570:
Tchaikovski SN, Rosing J (July 2010). "Mechanisms of estrogen-induced venous thromboembolism".
100:
1569:
1559:
1377:
159:
82:(in the lung, which can cause death). The most common cause of hereditary APC resistance is
1325:
1220:
1210:
244:
240:
115:
75:
424:
Nicolaes GA, Dahlbäck B (2003). "Congenital and acquired activated protein C resistance".
8:
1564:
1554:
1350:
1230:
248:
185:
143:
326:"Activated protein C resistance: the most common risk factor for venous thromboembolism"
1690:
1372:
1330:
1304:
1177:
1026:
Nichols WL, Heit JA (September 1996). "Activated protein C resistance and thrombosis".
1001:
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factor V Leiden, and people with heterozygous factor V Leiden who have an additional
71:
44:
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147:
83:
1710:
1422:
1365:
1247:
667:
513:
Hotoleanu, Cristina (2016). "Genetic Risk
Factors in Venous Thromboembolism".
342:
325:
1751:
1720:
1542:
1537:
1532:
1289:
798:
Clark P (February 2003). "Changes of hemostasis variables during pregnancy".
548:
530:
394:
232:
188:. There are two types of APC resistance tests with different properties: the
1463:
605:
Hemelaar M, van der Mooren MJ, Rad M, Kluft C, Kenemans P (September 2008).
1730:
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997:
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28:
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139:
131:
111:
The disorder can be acquired or inherited, the hereditary form having an
860:
767:
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1655:
1299:
1281:
228:
216:
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517:. Vol. 906. Springer International Publishing. pp. 253–272.
74:(blood clots in veins), which resulting in medical conditions such as
1705:
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155:
112:
67:
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1609:
1084:
832:
649:
Morimont L, Haguet H, Dogné JM, Gaspard U, Douxfils J (2021).
604:
372:
648:
134:. APC resistance is the inability of protein C to cleave
748:
930:
1150:
749:
Reda S, Morimont L, Douxfils J, RĂĽhl H (August 2020).
170:, have been found to produce acquired APC resistance.
702:
1062:
204:
Asymptomatic individuals with APC resistance (e.g.,
569:
277:"The discovery of activated protein C resistance"
1749:
423:
744:
742:
698:
696:
1021:
1019:
1017:
1015:
644:
642:
459:
457:
455:
1136:
515:Advances in Experimental Medicine and Biology
211:) are not normally treated unless additional
959:
924:
883:
826:
791:
739:
693:
506:
126:APC (with protein S as a cofactor) degrades
1025:
1012:
639:
598:
563:
452:
323:
1143:
1129:
274:
258:therapy followed by oral anticoagulation.
27:
987:
907:
850:
766:
676:
666:
622:
512:
481:
341:
292:
184:APC resistance can be evaluated using an
99:An estimated 64 percent of patients with
463:
94:
1397:
1750:
142:, which allows for longer duration of
1124:
797:
247:), should be considered for lifelong
22:Activated protein C resistance (APCR)
223:, in which perioperative short-term
180:Activated protein C resistance test
13:
227:may be used. However, people with
121:
14:
1774:
1058:
624:10.1016/j.fertnstert.2007.07.1298
1497:platelet storage pool deficiency
1449:Heparin-induced thrombocytopenia
980:10.1111/j.1538-7836.2005.01430.x
294:10.1046/j.1538-7836.2003.00016.x
219:are also present. An example is
190:activated partial thromboplastin
466:"Factor V Leiden thrombophilia"
89:
37:Protein C Anticoagulant Pathway
1216:Activated protein C resistance
584:10.1016/j.thromres.2010.01.045
417:
366:
317:
268:
56:Activated protein C resistance
1:
945:10.1016/j.transci.2017.11.021
387:10.1016/S0140-6736(05)80081-9
261:
194:endogenous thrombin potential
1310:Trousseau sign of malignancy
483:10.1097/GIM.0b013e3181faa0f2
464:Kujovich JL (January 2011).
199:
173:
7:
1763:Defects of enzyme cofactors
1630:Nonthrombocytopenic purpura
1206:Antithrombin III deficiency
655:Front Endocrinol (Lausanne)
152:Antiphospholipid antibodies
106:
10:
1779:
1585:Congenital afibrinogenemia
1489:Glanzmann's thrombasthenia
192:(aPTT)-based test and the
177:
1701:Gastrointestinal bleeding
1640:
1597:
1518:
1503:Hermansky–Pudlak syndrome
1462:
1404:
1390:
1318:
1280:
1272:Antiphospholipid syndrome
1253:Essential thrombocythemia
1193:
1186:
1163:
1066:
668:10.3389/fendo.2021.769187
343:10.3122/15572625-13-2-111
103:may have APC resistance.
78:(usually in the leg) and
43:
35:
26:
21:
1671:Subconjunctival bleeding
1477:Bernard–Soulier syndrome
1440:Upshaw–Schulman syndrome
1414:Thrombocytopenic purpura
1243:Sticky platelet syndrome
1661:Intracranial hemorrhage
896:J Clin Endocrinol Metab
237:antithrombin deficiency
158:, and certain forms of
1575:Factor XIII deficiency
1555:Hypoprothrombinemia/II
1550:von Willebrand disease
1508:Gray platelet syndrome
909:10.1210/jc.2003-030520
717:10.1055/s-0040-1714140
101:venous thromboembolism
1570:Factor XII deficiency
1560:Factor VII deficiency
1378:Renal vein thrombosis
523:10.1007/5584_2016_120
381:(8886–8887): 1503–6.
118:inheritance pattern.
95:Associated conditions
1326:Deep vein thrombosis
1221:Protein S deficiency
1211:Protein C deficiency
812:10.1055/s-2003-38329
438:10.1055/s-2003-38331
330:J Am Board Fam Pract
324:Sheppard DR (2000).
245:protein S deficiency
241:protein C deficiency
76:deep vein thrombosis
1565:Factor X deficiency
1454:May–Hegglin anomaly
1231:Prothrombin G20210A
768:10.1055/a-1153-5824
705:Semin Thromb Hemost
275:Dahlbäck B (2003).
186:APC resistance test
168:birth control pills
144:thrombin generation
1691:Pulmonary hematoma
1598:Signs and symptoms
1373:Pulmonary embolism
1178:Bleeding diathesis
933:Transfus Apher Sci
281:J. Thromb. Haemost
196:(ETP)-based test.
80:pulmonary embolism
64:hypercoagulability
1745:
1744:
1741:
1740:
1593:
1592:
1580:Dysfibrinogenemia
1464:Platelet function
1386:
1385:
1265:Purpura fulminans
1118:
1117:
852:10.1111/and.12150
540:978-3-319-22107-6
235:condition (e.g.,
162:therapy, such as
72:venous thrombosis
53:
52:
16:Medical condition
1770:
1406:Thrombocytopenia
1402:
1401:
1395:
1394:
1351:Lowenberg's sign
1201:Clotting factors
1191:
1190:
1145:
1138:
1131:
1122:
1121:
1064:
1063:
1052:
1051:
1040:10.4065/71.9.897
1023:
1010:
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991:
968:J Thromb Haemost
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164:ethinylestradiol
31:
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1768:
1767:
1748:
1747:
1746:
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1686:Hemopericardium
1636:
1589:
1520:Clotting factor
1514:
1458:
1382:
1331:Bancroft's sign
1314:
1305:Virchow's triad
1276:
1226:Factor V Leiden
1182:
1159:
1149:
1119:
1114:
1113:
1075:
1061:
1056:
1055:
1024:
1013:
964:
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884:
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827:
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755:Hamostaseologie
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541:
511:
507:
462:
453:
422:
418:
371:
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322:
318:
273:
269:
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225:anticoagulation
209:factor V Leiden
202:
182:
176:
148:Factor V Leiden
124:
122:Pathophysiology
109:
97:
92:
84:factor V Leiden
17:
12:
11:
5:
1776:
1766:
1765:
1760:
1758:Coagulopathies
1743:
1742:
1739:
1738:
1736:
1735:
1734:
1733:
1725:
1724:
1723:
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1711:Hemoperitoneum
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1479:
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1466:
1460:
1459:
1457:
1456:
1451:
1445:
1444:
1443:
1442:
1437:
1427:
1426:
1425:
1423:Evans syndrome
1410:
1408:
1399:
1392:
1388:
1387:
1384:
1383:
1381:
1380:
1375:
1370:
1369:
1368:
1363:
1358:
1356:Peabody's sign
1353:
1348:
1343:
1338:
1333:
1322:
1320:
1316:
1315:
1313:
1312:
1307:
1302:
1297:
1292:
1286:
1284:
1278:
1277:
1275:
1274:
1269:
1268:
1267:
1257:
1256:
1255:
1250:
1248:Thrombocytosis
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1235:
1234:
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1228:
1223:
1218:
1213:
1208:
1197:
1195:
1188:
1184:
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1160:
1148:
1147:
1140:
1133:
1125:
1116:
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1111:
1100:
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1076:
1071:
1070:
1068:
1067:Classification
1060:
1059:External links
1057:
1054:
1053:
1028:Mayo Clin Proc
1011:
974:(7): 1488–94.
958:
939:(6): 906–913.
923:
902:(12): 5723–9.
882:
825:
800:Semin Vasc Med
790:
761:(3): 364–378.
738:
711:(8): 872–886.
692:
638:
597:
562:
539:
505:
451:
426:Semin Vasc Med
416:
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1721:Hematosalpinx
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1374:
1371:
1367:
1364:
1362:
1359:
1357:
1354:
1352:
1349:
1347:
1346:Louvel's sign
1344:
1342:
1341:Lisker's sign
1339:
1337:
1334:
1332:
1329:
1328:
1327:
1324:
1323:
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1311:
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1291:
1290:Thrombophilia
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1199:
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1158:
1154:
1151:Disorders of
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617:(3): 642–72.
616:
612:
611:Fertil Steril
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233:thrombophilic
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187:
181:
171:
169:
165:
161:
157:
153:
149:
145:
141:
137:
133:
129:
119:
117:
114:
104:
102:
87:
85:
81:
77:
73:
69:
65:
61:
57:
48:
46:
42:
38:
34:
30:
25:
20:
1731:Hemarthrosis
1495:
1483:
1471:
1361:Pratt's sign
1215:
1173:coagulopathy
1102:
1091:
1079:
1034:(9): 897–8.
1031:
1027:
971:
967:
961:
936:
932:
926:
899:
895:
885:
861:11585/413984
845:(7): 791–5.
842:
838:
828:
806:(1): 13–24.
803:
799:
793:
758:
754:
708:
704:
658:
654:
614:
610:
600:
575:
571:
565:
514:
508:
473:
469:
432:(1): 33–46.
429:
425:
419:
378:
374:
368:
336:(2): 111–5.
333:
329:
319:
284:
280:
270:
213:risk factors
206:heterozygous
203:
183:
166:-containing
140:Factor VIIIa
132:Factor VIIIa
125:
110:
98:
90:Presentation
59:
55:
54:
36:
1484:aggregation
1366:Rose's sign
1336:Homans sign
1168:Coagulation
578:(1): 5–11.
476:(1): 1–16.
253:intravenous
1752:Categories
1716:Hematocele
1681:Hemothorax
1656:Hemoptysis
1528:Hemophilia
1300:Thrombosis
839:Andrologia
661:: 769187.
572:Thromb Res
287:(1): 3–9.
262:References
229:homozygous
217:thrombosis
178:See also:
86:mutation.
49:Hematology
1706:Hemobilia
1651:Epistaxis
1238:Platelets
989:1887/5044
785:220878363
733:224821517
549:0065-2598
531:2214-8019
500:220861191
470:Genet Med
395:0140-6736
200:Treatment
174:Diagnosis
156:pregnancy
136:Factor Va
128:Factor Va
113:autosomal
68:protein C
45:Specialty
1697:abdomen
1620:Petechia
1615:Hematoma
1605:Bleeding
1472:adhesion
1398:By cause
1391:Bleeding
1295:Thrombus
1194:By cause
1187:Clotting
1157:clotting
1153:bleeding
1088:: D68.51
1006:23567724
998:15978106
953:29162399
918:14671159
869:23944849
820:15199489
777:32726831
725:33080636
687:34956081
633:17923128
592:20163835
557:27638626
492:21116184
446:15199491
411:54283312
360:20016675
352:10764192
303:12871530
160:estrogen
116:dominant
107:Genetics
1666:Hyphema
1641:By site
1625:Purpura
1319:By site
1109:D020016
1048:8790269
877:5363824
678:8697849
403:7902898
311:2147784
256:heparin
221:surgery
138:and/or
62:) is a
1727:joint
1677:torso
1610:Bruise
1533:A/VIII
1098:188055
1046:
1004:
996:
951:
916:
875:
867:
818:
783:
775:
731:
723:
685:
675:
631:
590:
555:
547:
537:
529:
498:
490:
444:
409:
401:
393:
375:Lancet
358:
350:
309:
301:
1647:head
1282:Clots
1002:S2CID
873:S2CID
781:S2CID
729:S2CID
527:eISSN
496:S2CID
407:S2CID
356:S2CID
307:S2CID
243:, or
1543:C/XI
1538:B/IX
1155:and
1104:MeSH
1093:OMIM
1044:PMID
994:PMID
949:PMID
914:PMID
865:PMID
816:PMID
773:PMID
721:PMID
683:PMID
629:PMID
588:PMID
553:PMID
545:ISSN
535:ISBN
488:PMID
442:PMID
399:PMID
391:ISSN
348:PMID
299:PMID
249:oral
215:for
130:and
60:APCR
1435:TTP
1418:ITP
1260:DIC
1081:ICD
1036:doi
984:hdl
976:doi
941:doi
904:doi
857:hdl
847:doi
808:doi
763:doi
713:doi
673:PMC
663:doi
619:doi
580:doi
576:126
519:doi
478:doi
434:doi
383:doi
379:342
338:doi
289:doi
1754::
1430:TM
1416::
1107::
1096::
1085:10
1042:.
1032:71
1030:.
1014:^
1000:.
992:.
982:.
970:.
947:.
937:56
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912:.
900:88
898:.
894:.
871:.
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814:.
802:.
779:.
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753:.
741:^
727:.
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709:46
707:.
695:^
681:.
671:.
659:12
657:.
653:.
641:^
627:.
615:90
613:.
609:.
586:.
574:.
551:.
543:.
533:.
525:.
494:.
486:.
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468:.
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428:.
405:.
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354:.
346:.
334:13
332:.
328:.
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297:.
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239:,
154:,
1144:e
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1130:v
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285:1
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