Pulmonary thromboendarterectomy in a case of hereditary stomatocytosis

B. Murali1, A. Drain2, D. Seller3, J. Dunning2 and A. Vuylsteke*,1

1 Department of Cardiothoracic Anaesthesia, 2 Department of Cardiothoracic Surgery and 3 Cambridge Perfusion Services, Papworth Hospital, Cambridge CB3 8RE, UK

Corresponding author. E-mail: alain.vuylsteke@papworth.nhs.uk

Accepted for publication: June 2, 2003


    Abstract
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
We present a case of pulmonary thromboendarterectomy performed successfully in a patient with stomatocytosis. Stomatocytosis is a rare condition of abnormal erythrocyte morphology in which haemolysis and hyperkalaemia occur at cooler temperatures. A 35-yr-old male with stomatocytosis was referred for pulmonary thromboendarterectomy in the context of chronic thromboembolic pulmonary hypertension. He had undergone splenectomy as a child, which rendered him hypercoagulable as the spleen normally removes the haemolysed red cell fragments from blood. By constantly monitoring urine for macroscopic haematuria, arterial and mixed venous blood gas analysis perioperatively and by limiting the period of deep hypothermic circulatory arrest that is normally required for this operation, we were able to perform the operation successfully.

Br J Anaesth 2003; 91: 739–41

Keywords: blood, haemolysis; complications, chronic thromboembolic pulmonary hypertension (CTEPH); complications, hyperkalaemia; complications, hypothermia; complications, stomatocytosis; surgery, pulmonary thromboendarterectomy (PTE)


    Introduction
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious disease that induces hypoxaemia and pulmonary hypertension, eventually leading to respiratory insufficiency and right heart failure.1 Pulmonary thromboendarterectomy, the surgical treatment of pulmonary hypertension secondary to chronic pulmonary thromboembolic disease, requires cardiopulmonary bypass with deep hypothermic circulatory arrest. We present the first reported case of pulmonary thromboendarterectomy in a patient with hereditary stomatocytosis, a rare haemolytic blood disorder in which the red cell abnormalities are exacerbated by cooling.


    Case report
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
A 35-yr-old male was referred for pulmonary thromboendarterectomy after chronic thromboembolic pulmonary hypertension. He was well until the age of 28 yr, when he developed increasing shortness of breath on exertion. A diagnosis of pulmonary embolism was made and he was treated with warfarin for 6 months. Six weeks after the discontinuation of warfarin, he developed another pulmonary embolus, which was again treated with warfarin. He had an inferior vena cava filter inserted 4 yr later because of the development of progressively worsening CTEPH. He was started on diuretics and nebulized prostacyclin. He was referred for pulmonary thromboendarterectomy with a resting pulmonary arterial pressure of 103/26 (mean 56) mm Hg, with elevated central venous pressure and peripheral oedema, indicative of right ventricular failure.

He underwent prophylactic splenectomy because of a family history of hereditary spherocytosis at 5 yr of age. However, he was subsequently diagnosed as having hereditary stomatocytosis, activated protein C resistance and factor V Leiden mutation, and was positive for anticardiolipin antibody.

Anaesthetic management
The patient did not receive any premedication. The left radial artery was cannulated under local anaesthetic and the arterial blood pressure was monitored directly. Other monitoring included ECG, pulse oximetry, capnography and bispectral index. A 14-gauge cannula was inserted into a right forearm vein. General anaesthesia was induced with midazolam 5 mg, fentanyl 1 mg and propofol infused at the rate of 600 mg h–1 (10 mg kg–1 h–1) until loss of verbal contact and then infused at the rate of 300–500 mg h–1. Pancuronium 12 mg was used for neuromuscular block. The trachea was intubated using a size 9.0 cuffed endotracheal tube. A triple-lumen central venous line and a pulmonary artery flotation catheter were introduced through the right internal jugular vein. The pulmonary artery pressures were 88/33 (mean 51) mm Hg when measured preoperatively. A right femoral artery 18-gauge cannula was also sited to measure the arterial blood pressure. Dopamine was commenced at the rate of 3 µg kg–1 min–1 to support the failing right ventricle. Aprotinin was given as a bolus of 2 million k.i.u. followed by an infusion of 500 000 k.i.u. h–1. Vitamin K 10 mg was given to neutralize the anticoagulant effect of warfarin. Methylprednisolone 125 mg and antibiotics were administered according to local guidelines for the management of pulmonary thromboendarterectomy. Heparin 400 U kg–1 was given before cannulation of the aorta. The thromboelastograph trace, kaolin activated clotting time, mixed venous oxygen saturation, and arterial and mixed venous blood gas analysis were monitored at regular intervals before and during cardiopulmonary bypass.

Surgical technique and cardiopulmonary bypass management
After a median sternotomy, cardiopulmonary bypass was established using aortic cannulation, and a right atrial/innominate vein venous cannulation technique. Superior pulmonary vein and pulmonary artery vents were used. The pulmonary artery was opened through two arteriotomies. The right main pulmonary artery was approached between the superior vena cava and the aorta, while the left main pulmonary artery was opened longitudinally from the pulmonary trunk to the pleural reflection, as described previously.2 The patient was cooled and at 24°C was noticed to have developed macroscopic haematuria and a rise in serum K+ concentration (5.5 mmol litre–1). Cooling continued to 20°C and the endarterectomy was performed (Fig. 1) under profound hypothermic circulatory arrest lasting 20 min. Thiopentone 2 g and mannitol 0.5 g kg–1 were added to the pump before initiating circulatory arrest. When cooled below 24°C, the haematuria settled and there was a fall in serum K+ concentration to 2.76 mmol litre–1. After completion of the endarterectomy, the patient was rewarmed. The haematuria and the raised K+ concentration (5.74 mmol litre–1) returned at 24°C and again settled on completion of rewarming. The patient was weaned from cardiopulmonary bypass without any problems. Dopamine was continued at 3 µg kg–1 min–1. The effect of heparin was reversed with protamine. The total bypass time was 404 min, with an ischaemic time of 25 min.



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Fig 1 Endarterectomy specimen.

 
Postoperative management
The patient was returned to the intensive care unit (ICU) after the operation. All fluids and blood products were warmed before infusion. The pulmonary artery pressures had decreased to 54/26 (mean 36) mm Hg on the first postoperative day. The postoperative stay was complicated by reperfusion pulmonary oedema requiring diuretics and inhaled nitric oxide. No further episodes of haemolysis or hyperkalaemia were observed. Over the following week, inotropes and nitric oxide were weaned as cardiorespiratory function improved. Antibiotics based on microbial sensitivities were administered to treat a chest infection during the stay in the ICU. A tracheostomy was performed to facilitate weaning from the ventilator. The patient was successfully weaned off ventilatory support 2 weeks after the operation and was well enough to be discharged back to the ward on the 18th postoperative day. The tracheostomy tube was removed on the 20th postoperative day and the patient was discharged home a week later. Before discharge he mobilized well with physiotherapy support, and had no signs of elevated right atrial pressure. Peripheral blood oxygen saturation measured by pulse oximetry did not fall below 95% with exercise.


    Discussion
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Hereditary stomatocytosis is a rare autosomal dominant red cell membrane protein disorder, which results in haemolytic anaemia. It is so named because of the characteristic mouth shape of the erythrocytes. It is characterized by plasma membrane leakage of the univalent cations sodium (Na+) and potassium (K+).3 In some individuals with these disorders, bizarre temperature effects can occur that have profound effects on the way in which the cells behave when removed from the body and are cooled to either room or refrigerator temperature (so-called cryohydrocytosis). In some types, the cells lose K+ at room temperature, giving rise to pseudohyperkalaemia; in others, this occurs in concert with swelling of the red cell and pseudomacrocytosis. In some of these conditions, a red cell abnormality is clearly demonstrated by the presence of haemolytic anaemia; however, routine haematology can be virtually normal in the milder versions.

A review of published studies of the temperature effects in stomatocytosis showed very major differences in the leak K+ transport.4 Two main variations on normal emerge: a ‘shallow slope’ type, in which the flux shows an abnormally low dependence on temperature in the range 37–20° C, and ‘high minimum’, in which the minimum of this flux, which occurs in normal cells at 8° C, is increased to 23° C. The K+ leak and red cell lysis are exacerbated by reduced temperature. The abnormal temperature dependence in these genetically abnormal red cells strongly resembles that seen in normal cells when suspended in media in which either Na+ or Cl has been replaced by an organic cation or anion. These cells have a genetic mutation that renders them resistant to the stabilizing action of NaCl at low temperatures.5

Recent data suggest that hereditary stomatocytosis carries a high risk of thrombotic complications, especially after splenectomy.6 7 Usually the spleen acts to remove the red cell fragments after haemolysis. However, after splenectomy the risk of thrombosis is greatly increased in these patients and most of the symptoms represent vaso-occlusion secondary to adherence of the abnormal erythrocyte membrane to the vascular endothelium. Moreover, this patient presented with an extensive list of genetic risk factors that have been proven to increase susceptibility to venous thrombosis.8 The perioperative management routinely includes early and aggressive anticoagulation, initially with therapeutic doses of low molecular weight heparin, followed by warfarin.

Pulmonary thromboendarterectomy is a well-established procedure for the treatment of pulmonary hypertension secondary to chronic thromboembolism and is the surgical procedure of choice for patients with this condition. It has a perioperative mortality that compares favourably with lung transplantation. The long-term benefits of this procedure exceed those of both long-term medical treatment and transplantation. It provides a curative alternative to an otherwise fatal condition.9 This is the first report of successful pulmonary thromboendarterectomy in stomatocytosis. In this case, the increased membrane permeability to K+ and red cell lysis were demonstrated at 24° C, by haematuria and hyperkalaemia, resolving again at lower and higher temperatures. Despite this, the patient in our case report did remarkably well during the perioperative period. This case demonstrates that deep hypothermic circulatory arrest and pulmonary thromboendarterectomy can be performed successfully in patients with hereditary stomatocytosis if appropriate monitoring and care are taken.


    References
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
1 Fedullo PF, Auger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med 2001; 345: 1465–72[Free Full Text]

2 Jamieson SW, Auger WR, Fedullo PF, et al. Experience and results of 150 pulmonary thromboendarterectomy operations over a 29 month period. J Thorac Cardiovasc Surg 1993; 106: 116–27[Abstract]

3 Chetty MC, Stewart GW. Pseudohyperkalaemia and pseudomacrocytosis caused by inherited red-cell disorders of the ‘hereditary stomatocytosis’ group. Br J Biomed Sci 2001; 58: 48–55[ISI][Medline]

4 Coles SE, Stewart GW. Temperature effects on cation transport in hereditary stomatocytosis and allied disorders. Int J Exp Pathol 1999; 80: 251–8[CrossRef][ISI][Medline]

5 Cloes SE, Chetty MC, Ho MM, et al. Two British families with variants of the ‘cryohydrocytosis’ form of hereditary stomatocytosis. Br J Haematol 1999; 105: 1055–65[CrossRef][ISI][Medline]

6 Perel Y, Dhermy D, Carrere A, et al. Portal vein thrombosis after splenectomy for hereditary stomatocytosis in childhood. Eur J Pediatr 1999; 158: 628–30[CrossRef][ISI][Medline]

7 Delaunay J, Stewart G, Iolascon A. Hereditary dehydrated and overhydrated stomatocytosis: recent advances. Curr Opin Hematol 1999; 6: 110–4[CrossRef][Medline]

8 Franco RF, Reitsma PH. Genetic risk factors of venous thrombosis. Hum Genet 2001; 109: 369–84[CrossRef][ISI][Medline]

9 Dunning J, McNeil K. Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Thorax 1999; 54: 755–6[Free Full Text]