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Table of Contents
CASE REPORT  
Year : 2021  |  Volume : 24  |  Issue : 3  |  Page : 375-377
An unusual cause of heparin resistance - A case report


1 Department of Cardiothoracic and Vascular Surgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India
2 Department of Cardiac Anaesthesia, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India

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Date of Submission26-Dec-2019
Date of Decision25-Mar-2020
Date of Acceptance07-May-2020
Date of Web Publication09-Jul-2021
 

   Abstract 


Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals that result in leakage of excessive serum proteins and lymphocytes into the gastrointestinal (GI) tract culminating in protein-losing enteropathy. The GI loss of protein and possible antithrombin III (AT-III) loss creates a prothrombotic environment. The surgical management of congenital heart disease (CHD) in presence of PIL can present with altered heparin response and can impose problems in instituting cardiopulmonary bypass (CPB). We report a case of surgical closure of ventricular septal defect with PIL with altered heparin response. Such an association of PIL with altered heparin response in CHD has not been reported in literature.

Keywords: Altered heparin response, congenital heart disease, intestinal lymphangiectasia

How to cite this article:
Raja J, Baruah SD, Santhosh V, Menon S, Dharan BS. An unusual cause of heparin resistance - A case report. Ann Card Anaesth 2021;24:375-7

How to cite this URL:
Raja J, Baruah SD, Santhosh V, Menon S, Dharan BS. An unusual cause of heparin resistance - A case report. Ann Card Anaesth [serial online] 2021 [cited 2021 Oct 18];24:375-7. Available from: https://www.annals.in/text.asp?2021/24/3/375/320949





   Introduction Top


Altered heparin response is not uncommon in congenital heart disease (CHD), and the incidence varies over a wide range from 4 to 26%.[1] The ideal minimal and targeted activated clotting time (ACT) still remains elusive as there is a wide variation in institutional practice.[2] AT-III deficiency congenital or acquired has been implicated as the commonest cause of altered heparin response. Though extensive evaluation of biological defects in congenital AT-III have been done, the physiological and clinical consequences of acquired AT-III largely still remain unclear.[3]

Primary intestinal lymphangiectasia (PIL), a cause of protein losing enteropathy (PLE), is characterized by dilated intestinal lymphatic structures leading to excessive protein and lymphocyte loss in gastrointestinal (GI) tract. The proposed hypercoagulable state in PIL leading to venous thrombosis and embolic events is attributed to the intestinal loss of coagulation factors and AT-III. Though no direct association of PIL and CHD has been established nor altered heparin response in such a case has been described in literature, its concurrent presence may need careful consideration prior surgery to avoid any mishap during CPB.


   Case Report Top


A 6-year-old male child weighing 15 kg with the diagnosis of ventricular septal defect with mild aortic regurgitation following right coronary cusp prolapse was admitted for surgical repair [Figure 1]a and [Figure 1]b. The past history revealed history of abdominal distension, chronic diarrhoea, pedal edema, and recurrent carpopedal spasm. The blood investigations showed normal hemogram with normal renal function tests. The liver function test demonstrated total protein 3.6 gm/dl with serum albumin 1.6 gm/dl. The liver enzymes and coagulation profile were normal. The child was diagnosed with intestinal lymphangiectasia following duodenal biopsy. The child was managed conservatively with 20% albumin infusion, injection cholecalciferol along with oral calcitriol, calcium and magnesium supplements. The serum albumin improved to 2.4 gm/dl prior admission.
Figure 1: (a) TEE showing small restrictive ventricular septal defect with right coronary cusp prolapse. (b) TEE demonstrating mild aortic regurgitation. Ao: Aorta, LV: Left ventricle, VSD: Ventricular septal defect, AR: Aortic regurgitation

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During surgery, systemic heparinization was initiated with a dose of 500 U/kg and ACT at 3 minutes was measured as 286 seconds. A repeat dose of 400 U/kg heparin improved the ACT to 305 seconds. A total of, 200 ml of fresh frozen plasma (FFP) was infused; however, the ACT was still subtherapeutic (265 seconds). Further dose of 300 U/kg heparin achieved an ACT of 501 seconds. CPB was instituted, and routine VSD closure was done. ACT measured after half an hour of CPB was 414 seconds, and hence additional dose of 300 U/kg heparin was repeated that improved the ACT to 470 seconds. VSD closure was proceeded accepting slightly lower ACT with a short cross clamp time of 35 minutes and CPB time of 57 minutes.


   Discussion Top


Heparin exerts its anticoagulant effect by binding with AT-III, which is an endogenous glycoprotein produced by the liver. Heparin potentiates the action of AT-III 1000-fold on thrombin by forming an irreversible Heparin-ATIII-thrombin complex.[1]

PIL leads to a prothrombotic hypercoagulable state. Various mechanisms for such a physiological mileu have been postulated. The excessive enteric loss of albumin and AT-III along with the immunodeficiency state in the presence of an acute phase reactant protein is the widely accepted hypothesis.[4] Also, significant decrease in the AT-III level is noted when albumin level is <3 gm/dl.[5] The major consequences following such a state leads to an increased thrombotic risk with altered heparin response. Isolated case reports of incidence of arterial and pulmonary thrombosis requiring higher doses of heparin in PIL have been documented.[6],[7] Left-middle cerebral artery stroke in a PIL patient[8] further strengthens our suspicion that a patients with PIL do exhibit an altered heparin response.

The preoperative goal in this subset of patient should be directed toward improving serum albumin to normal range that also normalizes the AT-III level.[5] The serum transferrin has a similar short half-life as AT-III and can be a useful monitor to assess the AT-III level following nutritional support.[5] Dietary modification with medium chain triglyceride diet (MCT) forms the mainstay of therapy along with calcium, vitamin D, and fat soluble vitamins supplementation.[9],[10] Octreotide has also been used with success in some cases. Selective cases with very low albumin and the AT-III level may require preoperative therapy with AT concentrate based on AT activity. However, with good nutritional status, most of the cases can be managed with fresh frozen plasma to supplement AT-III for altered heparin response.

To conclude, altered heparin response should be anticipated in cases of PIL and should be managed aggressively with nutritional supplementation in order to prevent possible altered heparin response encountered during CPB. A larger group of patient with PIL/PLE should be evaluated with the AT-III level to further establish this association.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgments

No assistance taken from anybody for this work.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Finley A, Greenberg C. Heparin sensitivity and resistance: Management during cardiopulmonary bypass. Anesth Analg 2013;116:1210-22.  Back to cited text no. 1
    
2.
Lobato RL, Despotis GJ, Levy JH, Shore-Lesserson LJ, Carlson MO, Bennett-Guerrero E. Anticoagulation management during cardiopulmonary bypass: A survey of 54 North American institutions. J Thorac Cardiovasc Surg 2010;139:1665-6.  Back to cited text no. 2
    
3.
Prochoownik GV, Antonnarakis S, Bauer K, Rosenberg RD, Fearon ER, Orkin SH. Molecular heterogeneity of inherited antithrombin III deficiency. N Engl J Med 1983;308:1549-52.  Back to cited text no. 3
    
4.
Muntean W, Rossipal E. Loss of inhibitors of the blood coagulation system in protein losing enteropathy. Klinische Paediatrie 1979;191:20-3.  Back to cited text no. 4
    
5.
Flinn WR, McDaniel MD, Yao JST, Fahey VA, Green D. Antithrombin III deficiency as a reflection of dynamic protein metabolism in patients undergoing vascular reconstruction. J Vasc Surg 1984;1:888-95.  Back to cited text no. 5
    
6.
Durrani J, Malik F, Ali N, Jafri SIM. To be or not to be a case of heparin resistance. J Community Hosp Intern Med Perspect 2018;8:145-8.  Back to cited text no. 6
    
7.
Thandroyen FT, Phillips MD, D'Souza D, Buja LM. A 24-year-old man with extensive lower limb edema and acute arterial occlusion. Circulation 1994;90:2115-23.  Back to cited text no. 7
    
8.
Amtage F, Marouf W, Hetzel A, Schubert M. Acquired prothrombotic state due to protein-losing enteropathy as a rare cause for ischemic stroke? Eur J Neurol 2007;14:e7-8.  Back to cited text no. 8
    
9.
Koo, NH, Lee, HJ, Jung, JW. Primary intestinal lymphangiectasia: A response to medium-chain triglyceride formula. Acta Paediatr 2005;94:982-3.  Back to cited text no. 9
    
10.
Kim SJ, Park IS, Song JY, Lee JY, Shim WS. Reversal of protein-losing enteropathy with calcium replacement in a patient after Fontan operation. Ann Thorac Surg 2004;77:1456-7.  Back to cited text no. 10
    

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Correspondence Address:
Sudip D Baruah
Department of CTVS, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum - 695 011, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aca.ACA_197_19

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