A Case of Unexplained Cerebral Sinus Thrombosis in a 22-Year-Old Obese Caucasian Woman

Jansen N. Seheult, MB, BCh, BAO, MSc; Irina Chibisov, MD

Lab Med. 2016;47(3):223-240.

Final Diagnosis

We diagnosed the patient with extensive cerebral venous sinus thrombosis secondary to hypofibrinolysis, due to her homozygous PAI-1 4G/4G polymorphism and elevated PAI-1 antigen activity levels.

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Table 1. Results of Cerebrospinal Fluid Analysis of our Patient, a 22-Year-Old Obese Caucausian Woman
Test	Result/Units	Reference Range/Units
Opening pressure	31 cm H₂O	< 25 cm H₂O
Closing pressure	25 cm H₂O	< 15 cm H₂O
CSF appearance	Clear	NA
RBC count	58 mL	mL
WBC count	0 mL	mL
CSF glucose	67 mg/dL	40–75 mg/dL
CSF protein	25 mg/dL	15–45 mg/dL

NA, nonapplicable; RBC, red blood cells; WBC, white blood cells; CSF, cerebrospinal fluid.

Table 2. Results of Initial Laboratory Work-Up to Determine Presence or Absence of a Hypercoagulable State in Our Patient, a 22-Year-Old Obese Caucasian Woman
Test	Result/Units	Reference Range/Units
PT	10.7 s	9.8–11.5 s
INR	1.0	NA
APTT	21.8 s^a	30.0–42.0 s
TT	16.9 s	16.0–22.0 s
Factor VIII:C	5.54 U/mL^b	0.60–1.50 U/mL
dRVV ratio	1.1	0.9–1.3
Hexagonal phase lipid neutralization	Negative	Negative
TTI 1:50	1.1	0.7–1.3
TTI 1:500	1.0	0.7–1.3
Antithrombin III activity	114%	85%-140%
Protein C activity	64%^a	70%-150%
Protein S activity	80%	58%-128%
Beta-2-glycoprotein-I IgG	<9.4 SGU	<16.1 SGU
Beta-2-glycoprotein-I IgM	<9.4 SMU	<17.1 SMU
Beta-2-glycoprotein-I IgA	<9.4 SAU	<20.1 SAU
Anticardiolipin IgM	<9.4 MPL	<15.0 MPL
Anticardiolipin IgG	<9.4 GPL	<12.5 GPL
APC resistance ratio	2.6	2.1–3.0
Factor V leiden mutation	Negative	NA
Prothrombin gene G20210A variant	Negative	NA

PT, prothrombin time; INR, international normalized ratio; NA, nonapplicable; APTT, activated partial thromboplastin time; TT, thrombin time; dRVV, dilute Russell viper venom; TTI, tissue thromboplastin inhibition; Ig, immunoglobulin; SGU, standard IGM beta-2 glycoprotein unit; SMU, standard IgM beta-2 glycoprotein unit; SAU, standard IgA beta-2 glycoprotein unit; MPL, IgM phospholipid units; GPL, IgG phospholipid units; APC, activated protein C.
^aDenotes low value.
^bDenotes high value.

Table 3. Results of Testing of the Fibrinolytic Pathway in Our Patient, a 22-Year-Old Obese Caucasian Woman
Date	Test	Result/Units	Reference Range/Units
December 30, 2014	Plasminogen activity	144%	75%-150%
	PAI-1 activity^a	10.8 ng/mL	<5.0 ng/mL
	PAI-1 4G/5G testing^b	Homozygous for 4G/4G	5G/5G
	JAK2 V617F	Negative	NA
February 3, 2015	Protein C activity	96%	70%-150%
	PAI-1 activity	16.8 ng/mL	<5.0 ng/mL
June 24, 2015	PAI-1 activity	12.8 ng/mL	<5.0 ng/mL
	PAI-1 antigen^c	53.1 ng/mL	1.0–25.0 ng/mL

PAI, plasminogen activator inhibitor; JAK2, Janus kinase 2; NA, nonapplicable; ELISA, enzyme-linked immunosorbent assay.
^aPAI-1 activity level measured using the ZYMUTEST PAI-1 activity ELISA-based assay (Aniara Corporation).
^bPAI-1 4G/5G genotype determined using allele-specific polymerase chain reaction (PCR), as described by Falk et al in Cesarman-Maus et al.¹
^cPAI-1 antigen level measured using the ZYMUTEST PAI-1 antigen ELISA-based assay.