January 14, 2010

PET in Polycythemia Secondary to Pulmonary atresia and VSD with Compensated MAPCAS.

Partial Exchange Transfusion in Polycythemia Secondary to Pulmonary atresia and Ventricular Septal Defect with Compensated MAPCAS.

By: Muhamad Na’im B. Ab Razak

4th Year Medical Student, Universiti Sains Malaysia

Twelve years old Malay girl who is the youngest out of six siblings is born to a non- consangious parent, full term via emergency lower segment caesarian section because of maternal hypertension and one previous c-sec scar. Her weight at birth is 2.55 kg and she breast fed up to one year. This patient comes from a good socioeconomic family. Patient is a known case of complex cyanotic heart disease which has been diagnosed since she is five months old after the mother notice that her baby turns blue. Chest x ray shows boot shape heart. Echocardiography shows pulmonary atresia and ventricular septal defect. Native Pulmonary could not be visualized but there are multiple very small collateral vessels. Cardiac catherization shows no native pulmonary artery but there are multiple collaterals to both lungs. There are four main collaterals which are 1) from left carotid artery to upper and mid lobe of left lung, 2) from descending aorta to upper lobe of right lung, 3) from descending aorta to right lower lobe and 4) from abdominal aorta to right lower lobe. Due to her illness, patient no longer attends school and rest at home. Until now, patient is on conservative management and undergone partial exchange transfusion every four months. First partial exchange transfusion is on October 2003 and the last is on June 2009. Now, patient complaint of headache, loss of appetite, nausea and lethargy and cramping of the legs. Examination reveals central cyanosed, clubbing of the fingers and toes, and grade 3 Pan systolic murmur at left sternal edge. Full blood count shows Hb 21.9 g/dl, Hct 68.7%, Total white cell count 5.4 X 109/L and platelet count 221 X 109/L. SPO2 under normal air is 81%. She was then successfully undergone partial exchange transfusion of 400 ml blood.


Isolated pulmonary atresia with ventricular septal defect is a rare form of congenital heart disease, estimated to occur in 10.0/100 000 liveborn infants. The blood supply to the pulmonary arteries is provided by a patent arterial duct or by major aortopulmonary collateral arteries (MAPCAs), which can vary greatly in number and site of origin. [S Vesel et al]. The incidence is increase with the presence of chromosomal defect of 22q11.2 deletion.

Without treatment only about 10- 50% of children born with congenital anomalies of the heart or vascular system would survive beyond puberty. 20-25% died in the neonatal period and 50 to 60% died in the first year [Jane Somerville]. However, Medical and surgical advances have led to a dramatic decrease in mortality among patients with congenital heart disease, with the vast majority surviving to adulthood [D A Lane et al]

Erythrocytosis or polycythemia of chronic hypoxemia is a physiological response to tissue hypoxia whereby erythropoietin stimulates increase in production of circulating red blood cell by bone marrow in order to enhance oxygen carrying capacity. These will also resulting in increase erythrocyte mass, hematocrit and whole blood viscosity. Failure of this adaptive mechanism may impairs oxygen delivery and nullify the beneficial effect of erythrocytosis. The most common complication of blood hyperviscosity in cyanotic heart disease patient is cerebral infarction which is due to increase in biosynthesis of thromboxane A2 and increase in ratio of thromboxane A2 to prostacyclin that favors vasoconstriction and platelet aggregation.

Polycythaemic cyanotic patients experience symptoms caused by the detrimental effects of hyperviscosity on tissue oxygen delivery rather than by a high hematocrit itself. The symptoms include headache, faintness and dizziness, blurred vision, amaurosis fugax, fatigue, myalgia, muscle weakness, paraesthesia, depressed mentation, sense of distance and chest and abdominal pain. [S.A Thorne]

Traditionally, Polycythemia has been defined as a venous hematocrit over 65%. This cut off was chosen based on the observation that blood viscosity exponentially increased above a hematocrit of 65% [Soll R et al].

Erythrocytosis can be relieved by controlled venesection and appropriate volume replacement. However, overzealous in treatment or neglecting of volume replacement may give rise to problems. In such patients, thrombosis or hemorrhage readily develops in response to trauma. They may have gout (which may still be diagnosed as whitlows in some casualty departments); renal problems leading to anuria in response to fluid restriction; skin sepsis from chronic acne; and chronic arthropathy in the ankles and knees, which may be their major complaint. Relative anaemia, which may be caused by excessive venesection, gastric bleeding, or bad nutrition, may escape notice and cause worsening symptoms or heart failure in sinus rhythm [Jane Somerville]

According to P J Oldershaw, Acute reduction in hematocrit in patient with severe polycythemia secondary to cyanotic congenital heart disease resulted in an increase in resting cardiac output without alteration in heart rate. Cardiac output was also increased during a constant-load exercise test after hematocrit reduction, and under these conditions total oxygen uptake was increased with consequent reduction in oxygen debt

The “gold standard” measurement of viscosity uses a whole blood viscometer that can accurately measure the viscosity of blood at the low shear rates that occur naturally in the capillary circulation [Soll R et al]. However, since it is not widely available, therefore hematocrit measurement can be used as a screening test. Value of hematocrit over 65% can be an indicator to start Partial exchange transfusion (PET)

PET is traditionally used as the method to lower the hematocrit and treat hyperviscosity. PET is performed with either crystalloid (normal saline) or colloid (5% albumen) solutions. The volume to be exchanged is based on the observed and desired hematocrit (usually 55%). PET has been shown to reduce pulmonary vascular resistance and increase cerebral blood viscosity. [Soll R et al]. Volume to be exchanged may be calculated by using this simple equation

Volume (mL) = (Initial Hct – Desired Hct) x Patient’s Blood volume (i.e Weight (kg) x 80)

Initial Hct

Reported complications in whole blood exchange include infections, cardiac arrhythmia, thrombosis, emboli, vessel perforation, necrotizing enterocolitis, accidental hemorrhage, air embolus, hypothermia, reduction in blood pressure and cerebral blood flow fluctuation and even death. Full exchange transfusion is expected to have a higher incidence of complications than PET, since the amount of blood to be exchanged is almost nine times higher and the product utilized for the exchange is donor’s blood. Most of these complications can be avoided by performing the procedure carefully, while monitoring vital signs and adjusting to a standard protocol [Soll R et al]

According to Dempsey Eugene M et al, in choosing the fluid for PET, there is no reported important difference in short-term physiologic effects between crystalloid and colloid. Use of crystalloid was as effective as colloid in both correction of hematological values and reduction of clinical symptoms following partial exchange transfusion. When crystalloid solutions are used for this purpose, there is no risk of transmission of blood-borne diseases and anaphylaxis, rapid and easily available, and are less expensive.

Besides phlebotomy and partial exchange blood transfusion, study also shows other method to overcome polycythemia in Cyanotic Heart Disease patients. Ulrike M. Reiss et al has reported a successful approach in treating for patients by using hydroxyurea therapy. According to his literature, Hydroxyurea (hydroxycarbamide) is an S-phase specific chemotherapeutic agent that inhibits ribonucleotide reductase, and thus interferes with the production of DNA precursors required for cell replication and nuclear maturation. Hydroxyurea therapy for secondary erythrocytosis should therefore lower blood viscosity by reducing RBC count and hematocrit through marrow suppression, while simultaneously improving oxygen-carrying capacity per erythrocyte by increasing the MCV and MCH

There is a various surgical approach made by many centers to correct this congenital problems. However, long term prognosis at most medical centers has not been satisfactory. [JS Bang et al]

Other care for cyanotic heart disease patient includes to avoid hemoglobin concentration less than 10.6 mmol/l in patient with oxygen saturation <>

There is a need for intervention to improve the quality of life in cyanotic heart disease patient. A study done by D A Lane et al shows that patients with inoperable or cyanotic conditions and, paradoxically, those deemed surgically cured, had the poorest quality of life among adults with congenital heart disease. However, all adults with congenital heart disease had significantly poorer levels of physical functioning and overall general health perception then similarly aged people in the general population.

Download pdf [here]


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2) Dempsey Eugene M & Barrington Keith, "Crystalloid or colloid for partial exchange transfusion in neonatal polycythemia : A systematic review and meta-analysis", Acta paediatrica, vol. 94, Blackwell, 2005

3) F Walker, M J Mullen, S J Woods, et al, "Acute effects of 40% oxygen supplementation in adults with cyanotic congenital heart disease", Heart 2004 90: 1073-1074

4) Gary D Webb, "Challenges In The Care Of Adult Patients With Congenital Heart Defects", Heart 2003;89:465–469

5) I Adatia, S E Barrow, P Stratton, et al, "Abnormalities in the biosynthesis of thromboxane A2 and prostacyclin in children with cyanotic congenital heart disease", Heart 1993 69: 179-182

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7) Ji Seok Bang, Jae Suk Baek, Ling Zhu et al, "Pulmonary Atresia with Ventricular Septal Defect and Major Aorto-Pulmonary Collateral Arteries: Management Strategy at Our Hospital and the Results", Korean Circulation J 2007;37:348-352.

8) L Swan & W S Hillis, "Management of Polycythaemia in Adults With Cyanotic Congenital Heart Disease", Heart 1999, 81:4:451.

9) P J Oldershaw & M G St John Sutton, "Haemodynamic Effects Of Haematocrit Reduction In Patients With Polycythaemia Secondary to Cyanotic Congenital Heart Disease", Heart 1980; 44: 584-8

10) S A Thorne, "Management of Polycythemia in Adults With cyanotic Congenital Heart Disease", Heart 1998 79: 315-316

11) Soll R, Schimmel MS & Özek E. "Protocol on Partial Exchange Transfusion to Prevent Neurodevelopment Disability in Infants with Polycythemia", The Cochrane Library 2009, Issue 4, John Wiley & Sons, Ltd.

12) S Vesel, S Rollings, A Jones et al, "Prenatally diagnosed pulmonary atresia with ventricular septal defect: echocardiography, genetics, associated anomalies and outcome", Heart 2006;92:1501–1505

13) Ulrike M. Reiss, Pamela Bensimhon, Sherri A. Zimmerman & Russell E. Ware, "Hydroxyurea therapy for Management of Secondary Erythrocytosis in Cyanotic Congenital Heart Disease", American Journal of Hematology, Wiley-Liss, Inc, 2007

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