|Year : 2017 | Volume
| Issue : 3 | Page : 173-176
Hereditary thrombophilia (rare multiple genetic defects combination) caused portal vein thrombosis complicated by hypersplenism and pancytopenia
Sally S Eldin1, Nora I Abbas MD 1, Noha K Mohamed2, Aml S Nasr3
1 Department of Critical Care, Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||25-Sep-2016|
|Date of Acceptance||01-Mar-2017|
|Date of Web Publication||5-Jul-2017|
Nora I Abbas
Critical Care Department, Faculty of Medicine; Cairo University, Al-Saray Street, El Manial Cairo 11956
Source of Support: None, Conflict of Interest: None
Venous thrombosis is the third-ranking cardiovascular disease following only coronary heart disease and stroke . Venous thrombosis has an overall yearly incidence of less than 1 in 1000 . A middle-aged female patient without relevant medical history was admitted with syncope and pancytopenia to the critical care unit of Cairo University hospitals. Viral profile and renal and hepatic functions were normal, as well as bone marrow aspirate. Abdominal ultrasound followed by computed tomography of the abdomen showed moderate splenomegaly with no focal splenic lesions for clinical laboratory correlation and portal hypertension with portal vein cavernoma (mostly an organized old thrombosis during pregnancy) for color Doppler evaluation, which confirmed the diagnosis. Thrombophilia screening showed rare multiple thrombophilic genetic defects.
Keywords: antithrombin III deficiency, MTHFR deficiency, pancytopenia, thrombophilia, venous thromboembolism
|How to cite this article:|
Eldin SS, Abbas NI, Mohamed NK, Nasr AS. Hereditary thrombophilia (rare multiple genetic defects combination) caused portal vein thrombosis complicated by hypersplenism and pancytopenia. Res Opin Anesth Intensive Care 2017;4:173-6
|How to cite this URL:|
Eldin SS, Abbas NI, Mohamed NK, Nasr AS. Hereditary thrombophilia (rare multiple genetic defects combination) caused portal vein thrombosis complicated by hypersplenism and pancytopenia. Res Opin Anesth Intensive Care [serial online] 2017 [cited 2020 Jun 4];4:173-6. Available from: http://www.roaic.eg.net/text.asp?2017/4/3/173/209670
| Introduction|| |
To our knowledge, no such number and combination of thrombophilic genetic defects were reported, as well as the unusual initial presentation as pancytopenia due to hypersplenism resulting from portal vein thrombosis ,.
Congenital (hereditary) thrombophilia is classified as follows: major (type 1) thrombophilias, which are rare, and are typically caused by a deficiency of natural anticoagulants − they have more thrombotic tendency and include antithrombin III (ATIII) deficiency, protein C, and protein S deficiency ; and minor (type 2) thrombophilias, which are much more common, and they occur because of overactivity of coagulation factors including factor V Leiden, and prothrombin mutation .
Unclear conditions include elevated levels of factors VIII, IX, XI, and thrombin-activatable fibrinolysis inhibitor and decreased levels of tissue factor pathway inhibitor, as well as hyperhomocysteinemia . Homocysteine levels are determined by mutations in the MTHFR and cystathionine β synthase (CBS) genes, but also by levels of folic acid, vitamin B6, and vitamin B12, which depend on diet .
| Case presentation|| |
Portal vein thrombosis and hypersplenism due to thrombophilia with multiple gene defects
A 40-year-old married Egyptian female patient presented to the emergency department followed by medical ICU admission in Kasr El Eini University Hospital (Cairo, Egypt) with dizziness, drowsiness, and fainting on the day of admission. The condition started gradually since a long period with easy fatigability, lack of concentration, and weakness. She had no history of fever, cough, weight loss, subcutaneous nodules, or altered skin pigmentation. She worked as an ICU nursing morning staff. She was of gravida 3 para 3 with no complications during her deliveries. Her last delivery was 3 months ago. She denied smoking or drinking. Her past medical, medication, family, and allergy history was of insignificant importance. Cardiac examination was notable for tachycardia 105 beats/min but no gallops, rubs, or extracardiac sounds were observed. There was no evidence of jugular venous distension. Apart from tender soft splenomegaly (spleen is about 3 cm below the costal margin), her abdomen is soft, nontender, and nondistended with normal bowel sounds. She was alert, conscious, and cooperative, with average mood and memory and average intelligence. Examination revealed stable hemodynamic heart rate 105 beats/min, a blood pressure of 120/80, a temperature of 37°C, and ECG showed normal sinus rhythm. She was tall, 177 cm, with an average body weight, was apprehensive lying comfortably in bed, and without respiratory distress. She was pale but not cyanosed or jaundiced. No local or generalized pigmentation was observed. There was no thyroid enlargement and no lymphadenopathy. Rectal examination revealed no masses. Upper-limb and lower-limb pulses were felt without edema. Normal breath sounds were observed on chest examination. Neurological examination revealed no abnormality.
Normal reflexes were elicited. The results of the laboratory investigation were as follows: for pancytopenia, hemoglobin level was 6.6 g%; Total leucocytic count (TLC) was 2.9×109/L; platelets were 120×109/L; iron profile showed a level of 10 ng/dl (50–175 ng/dl); Total iron binding capacity (TIBC) was 427 (250–450 µg/dl); bilirubin was 1.2 and retics 2%; cytomegalovirus IgM equivocal 0.493 index; and IgG level was more than 250 IU/ml. Brucella More Details and typhoid serological tests were negative. Haptoglobin level was 64 mg/dl (the normal range is 41–165 mg/dl) and autoimmune profile, as well as hepatitis markers, was negative.
An abdominal ultrasound revealed average-sized uniform bright liver. There was no definite sonographic evidence of liver cirrhosis, portal vein cavernoma (mostly an organized old thrombosis during pregnancy), and moderate splenomegaly. Portal hypertension was present.
Abdominal ultrasound was followed by computed tomography abdomen, which showed moderate splenomegaly with no focal splenic lesions for clinical laboratory correlation. Suspected portal cavernoma for color Doppler evaluation which confirmed the diagnosis.
Upper gastrointestinal tract endoscope revealed three cord esophageal varices, grade II–III, for which prophylactic band ligation was performed in addition to congestive gastropathy.
Bone marrow aspirate
The bone marrow was hypercellular. Erythroid hyperplasia was present, with normal morphology and maturation and occasional dysplastic changes. Myeloid series showed normal morphology and maturation. Megakaryocytic series showed a normal number of lobulation and budding with the presence of marrow platelets. These results revealed a picture of a reactive bone marrow.
The following genetic abnormalities were revealed:
Protein C: 59% (N=82–110%).
Protein S: 100% (N=65–140%).
Factor V Leiden normal.
Prothrombin gene mutation normal.
ATTIII: 77% (N=83–111%).
CD55: 74.1%; control: 78.9%.
CD59: 95.1%; control: 81%.
Plasminogen activator inhibitor-1 (4G/4G genotype).
Human platelet antigen a/a genotyping.
MTHFR (A1298c) heterogeneous genotype.
Angiotensin-converting enzyme (ACE1/D) heterogeneous genotype ACE Del.
ApoE: E2/E3 heterogeneous.
From the day of admission and over the next six days, five blood units were transfused without complications until achieving hemoglobin level. The patient received iron replacement (1500 mg) as well. The patient was discharged home safely with follow-up and recommendation for thromboprophylaxis in the next pregnancy both antepartum and postpartum.
| Discussion and review of literature|| |
Protein C deficiency
Protein C deficiency is inherited in an autosomal dominant manner and is associated with familial venous thromboembolism (VTE) ,. Two major subtypes exist. Type I deficiency is more common. The affected patients have a reduced plasma protein C concentration at approximately 50% of normal in both immunologic and functional assays . In type II deficiency, plasma protein C antigen levels are normal with diminished function .
Protein C deficiency has been incriminated in adverse pregnancy outcomes such as Deep venous thrombosis (DVT), preeclampsia, and recurrent pregnancy loss . Protein C-deficient family members have 8- to 10-fold increased venous thrombosis tendency, and by age 40 50% or more will have suffered a thrombotic accident ,.
AT deficiency is usually inherited in an autosomal dominant manner.
- Type I: It is the result of diminished synthesis of biologically normal protease inhibitor molecules . In these cases, both the antigenic and functional AT activity in the blood are reduced by about 50% in the heterozygote .
- Type II: It is caused by a discrete molecular defect within the protein. Type II cases have normal AT immunologic activity and markedly reduced plasma AT functional activity.
- Type III: Cases with type III have normal functional and antigenic AT levels but impaired AT–heparin interaction .
Heparin binding site defect: In this defect, there are abnormal AT molecules with defective heparin binding site, resulting in isolated decrease in heparin cofactor activity . Patients have AT levels 40–60% of normal, and 70% of them experience thrombotic accident before the age of 50 years .
The lifetime thrombotic risk compared with normal subjects was 8.1 for type I ATIII deficiency and 7.3 for protein C deficiency .
Hyperhomocysteinemia is both a genetic (autosomal recessive) and acquired abnormality. Even mild hyperhomocysteinemia is an independent risk factor for VTE ,. Inherited hyperhomocysteinemia can be further exaggerated by deficiencies in vitamins B6, vitamin B12, and folic acid. It is classified into three categories according to the fasting homocysteine elevation: (i) severe (more than 100 mol/l), (ii) moderate (25–100 mol/l), or (iii) mild (16–24 mol/l) .
Plasminogen deficiency occurs in 0.5–2% of patients with a history of VTE with plasminogen concentration less than 40% of control values . Tissue plasminogen activator levels above normal (10 ng/ml) in VTE patients correlate with VTE recurrence . Elevated plasminogen activator inhibitor-1levels increase the risk of arterial thrombosis  and VTE recurrence .
ACE1/D heterogeneous genotype ACE Del. The ACE I/D polymorphism identifies genetic variants that may contribute to the risk of ischemic stroke through increased vasoconstriction, cellular hypertrophy, and thrombosis after an increase in angiotensinogen II levels and the inactivation of bradykinin .
Lp(a) reduces plasmin generation, and binds and inactivates tissue factor pathway inhibitor . Elevated levels of lipoprotein A (>300 mg/l) correlated independently with VTE . ApoE: E2/E3 heterogeneous genotype E2 is associated with high levels of factor VIII in plasma .
The ratio of developing MI or unstable angina between patients with the HPA-1a/1a genotype and those with either the HPA-1a/1b or the 1b/1b genotype was found to be 6 : 2 .
Our patient was discharged home and recommended to take thromboprophylaxis in the next pregnancy both antepartum and postpartum because she had DVT and was at high risk in her previous pregnancy , although she stated that it is not intended.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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