J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website http://www.thejh.org

Case Report

Volume 8, Number 4, December 2019, pages 155-159

Superwarfarin Exposure: An Important Uncommon Cause of Painless Bleeding

Figure 1. Inpatient course: INR in relation to treatment (plasma infusion: three units on the first day of hospitalization and one more unit on day 3). INR: international normalized ratio.

Figure 3. Mechanism of action of warfarin and superwarfarins. Brodifacoum and other superwarfarin similar to warfarin exert their effect by inhibiting VKOCR1. Inhibition of VKOCR1 leads to reduced bioavailability of the metabolically active reduced form of vitamin K resulting in decreased glutamyl carboxylation of vitamin K-dependent proteins including coagulation factors II, VII, IX and X, and protein S and C. S-warfarin and R-warfarin refer to S and R enantiomers of warfarin. VKORC1: vitamin K 2,3-epoxide reductase complex subunit 1.

**Table 1.** Initial Screening and Follow-up Studies
Analyte	Result (reference interval)
^aVitamin K dependent factors. PT: prothrombin time; aPTT: activated partial thromboplastin time; VWF: von Willebrand factor; APL: acute promyelocytic leukemia.
Initial screening tests
Prolonged PT evaluation	24.2 s (9 - 11.5)
PT immediate mix	11.7 s (9 - 11.5)
Prolonged aPTT evaluation	40 s (22 - 34)
aPTT immediate mix	28 s (22 - 34)
Follow-up studies
Procoagulant factors
Factor II activity^a	37% (70-150%)
Factor V activity	110% (65-150%)
Factor VII activity^a	< 1% (60-175%)
Factor VIII activity	152% (60-180%)
Factor IX activity^a	15% (50-160%)
Factor IX antigen^a	1.11 (0.64 - 1.29)
Factor X activity^a	27% (70-150%)
Factor XI activity	94% (65-150%)
Factor XII activity	92% (50-150%)
Von Willebrand factor antigen	146% (50-217%)
Ristocetin cofactor activity	82% (42-200%)
VWF multimeric study	Normal
Prothrombotic risk factors
ATIII antigen	130% (70-150%)
ATIII activity	125% (80-120%)
Protein C antigen^a	74% (70-140%)
Protein C activity^a	58% (70-180%)
Total protein S antigen^a	91% (70-140%)
Free protein S antigen^a	57% (57-171%)
APL studies (including lupus anticoagulant, cardiolipin and beta2-glycoprotein I antibodies)	Negative (negative)
Serum immunofixation studies	Negative (negative)
Brodifacoum (qualitative test)	Positive (negative)

Table 1. Initial Screening and Follow-up Studies

Analyte

Result (reference interval)

^aVitamin K dependent factors. PT: prothrombin time; aPTT: activated partial thromboplastin time; VWF: von Willebrand factor; APL: acute promyelocytic leukemia.

Initial screening tests

Prolonged PT evaluation

24.2 s (9 - 11.5)

PT immediate mix

11.7 s (9 - 11.5)

Prolonged aPTT evaluation

40 s (22 - 34)

aPTT immediate mix

28 s (22 - 34)

Follow-up studies

Procoagulant factors

Factor II activity^a

37% (70-150%)

Factor V activity

110% (65-150%)

Factor VII activity^a

< 1% (60-175%)

Factor VIII activity

152% (60-180%)

Factor IX activity^a

15% (50-160%)

Factor IX antigen^a

1.11 (0.64 - 1.29)

Factor X activity^a

27% (70-150%)

Factor XI activity

94% (65-150%)

Factor XII activity

92% (50-150%)

Von Willebrand factor antigen

146% (50-217%)

Ristocetin cofactor activity

82% (42-200%)

VWF multimeric study

Normal

Prothrombotic risk factors

ATIII antigen

130% (70-150%)

ATIII activity

125% (80-120%)

Protein C antigen^a

74% (70-140%)

Protein C activity^a

58% (70-180%)

Total protein S antigen^a

91% (70-140%)

Free protein S antigen^a

57% (57-171%)

APL studies (including lupus anticoagulant, cardiolipin and beta2-glycoprotein I antibodies)

Negative (negative)

Serum immunofixation studies

Negative (negative)

Brodifacoum (qualitative test)

Positive (negative)