UBP 4.1 (Short Form): Obstetrics - Sickle Cell Disease

Question 1

Why is she taking hydroxyurea?

(A 32-year-old, 99 kg, G4P3 female requires a repeat cesarean section due to severe preeclampsia. She is at 36 weeks gestation, with a history of three previous cesarean sections. The obstetrician informs you she does not know the patient and that there has been no prenatal care. She further reports shortness of breath with exertion and frequent hospital admissions due to pain from her sickle cell disease. Her surgical history consists of a splenectomy 18 years ago and retinal detachment surgery under local anesthesia 1 week ago. Her current medications include hydroxyurea and oxycodone. She reports taking narcotics routinely for the past couple of years and is afraid she is becoming addicted. Hgb = 7.8 g/dL. BP = 188/104 mmHg.)

Answer 1

Hydroxyurea is often administered to reduce the number of sickle cell crises via – its ability to increase circulating fetal hemoglobin, which, in turn, reduces the rate and extent of HbS sickling.

Some other mechanisms by which hydroxyurea may reduce the number of sick cell crises include – increases in nitric oxide, modification of the inflammatory response, and a reduction in the white blood cell count.

Question 2

What is the pathophysiology of Sickle Cell Disease?

(A 32-year-old, 99 kg, G4P3 female requires a repeat cesarean section due to severe preeclampsia. She is at 36 weeks gestation, with a history of three previous cesarean sections. The obstetrician informs you she does not know the patient and that there has been no prenatal care. She further reports shortness of breath with exertion and frequent hospital admissions due to pain from her sickle cell disease. Her surgical history consists of a splenectomy 18 years ago and retinal detachment surgery under local anesthesia 1 week ago. Her current medications include hydroxyurea and oxycodone. She reports taking narcotics routinely for the past couple of years and is afraid she is becoming addicted. Hgb = 7.8 g/dL. BP = 188/104 mmHg.)

Answer 2

Sickle cell disease (SCD) is a well-defined hemoglobinopathy in which a mutation of chromosome 11 results in the substitution of valine for glutamic acid in the beta chains of hemoglobin (resulting in HbS).

In the presence of decreased oxygen tension, hemoglobin S (HbS) molecules can polymerize, causing deformation of the red cell membrane into a sickled shape, which leads to –

• hemolysis (average red blood cell lifespan is 12-17 days instead of 120 days),
• microvascular occlusion of capillaries,
• ischemic end-organ injury,
• infarcts, and
• hemolytic crisis secondary to hemolysis.

Question 3

Why doesn’t sickling always occur in venous blood?

(A 32-year-old, 99 kg, G4P3 female requires a repeat cesarean section due to severe preeclampsia. She is at 36 weeks gestation, with a history of three previous cesarean sections. The obstetrician informs you she does not know the patient and that there has been no prenatal care. She further reports shortness of breath with exertion and frequent hospital admissions due to pain from her sickle cell disease. Her surgical history consists of a splenectomy 18 years ago and retinal detachment surgery under local anesthesia 1 week ago. Her current medications include hydroxyurea and oxycodone. She reports taking narcotics routinely for the past couple of years and is afraid she is becoming addicted. Hgb = 7.8 g/dL. BP = 188/104 mmHg.)

Answer 3

While HbS starts to polymerize at a PO2 of 50 mmHg, this process is time-dependent.

Therefore, even though venous blood normally has a PO2 of ~40 mmHg (SvO2 = ~75%),

only about 5% of HbS sickles while in transit to the lungs where oxygenation results in a reversal of much of erythrocyte sickling.

Question 4

The medical student finds out that the patient’s father experienced aplastic crisis when he was younger. What is aplastic crisis and how do you treat it?

(A 32-year-old, 99 kg, G4P3 female requires a repeat cesarean section due to severe preeclampsia. She is at 36 weeks gestation, with a history of three previous cesarean sections. The obstetrician informs you she does not know the patient and that there has been no prenatal care. She further reports shortness of breath with exertion and frequent hospital admissions due to pain from her sickle cell disease. Her surgical history consists of a splenectomy 18 years ago and retinal detachment surgery under local anesthesia 1 week ago. Her current medications include hydroxyurea and oxycodone. She reports taking narcotics routinely for the past couple of years and is afraid she is becoming addicted. Hgb = 7.8 g/dL. BP = 188/104 mmHg.)

Answer 4

Aplastic crisis results when – bone marrow suppression secondary to –

• infection (typically Parvovirus B19) or
• folate deficiency

– leads to decreased red blood cell production.

The depression of erythropoiesis combined with the reduced life-span of red blood cells in sickle cell patients (12-17 days vs. the normal 120 days), leads to profound anemia.

Treatment would involve the correction of any folate deficiency and the administration of blood until bone marrow suppression resolves (usually 4-7 days).

Question 5

How would you evaluate this patient pre-operatively?

(A 32-year-old, 99 kg, G4P3 female requires a repeat cesarean section due to severe preeclampsia. She is at 36 weeks gestation, with a history of three previous cesarean sections. The obstetrician informs you she does not know the patient and that there has been no prenatal care. She further reports shortness of breath with exertion and frequent hospital admissions due to pain from her sickle cell disease. Her surgical history consists of a splenectomy 18 years ago and retinal detachment surgery under local anesthesia 1 week ago. Her current medications include hydroxyurea and oxycodone. She reports taking narcotics routinely for the past couple of years and is afraid she is becoming addicted. Hgb = 7.8 g/dL. BP = 188/104 mmHg.)

Answer 5

GIven this patient’s sickle cell disease, I would:

1. investigate the severity and frequency of vaso-occlusive crisis (especially during pregnancy, since being pregnant often exacerbates complications);
2. inquire about any history of aplastic anemia, acute chest syndrome, hemolytic crisis, splenic sequestration crisis, or complications from transfusion;
3. identify any –
   
   • cardiac (i.e. CHF, cor pulmonale, myocardial infarction, arrhythmias),
   • pulmonary (i.e. sickle cell lung disease: pulmonary fibrosis, pulmonary hypertension, progressive hypoxia),
   • renal (i.e. renal insufficiency/failure, inability to concentrate urine), or
   • central nervous system involvement (i.e. stroke, seizures, subarachnoid hemorrhage);
4. examine the patient for signs of infection (infection increases the risk of perioperative complications associated with sickle cell disease);
5. evaluate the patient’s volume status, recognizing that adequate hydration is important to reduce the risk of sickling;
6. order pre and post-transfusion hematocrit, creatinine, blood urea nitrogen, and room air oximetry.
7. Moreover, given her shortness of breath, I would – order a chest radiograph, ECG, arterial blood gases, an echocardiogram, and pulmonary function tests.

Considering her preeclampsia and pregnancy, I would –

• perform a careful airway exam,
• check a platelet level (preeclampsia is associated with thrombocytopenia and thrombocytopathia),
• evaluate the patient for signs of coagulopathy (i.e. bleeding at IV sites and bruising),
• review her recent blood pressures, and
• check her fluid status (preeclamptic patients are often hypovolemic despite third spacing).

Finally, since she is obese, I would –

• ask about any history of obstructive sleep apnea,
• chronic hypertension,
• right or left ventricular failure,
• pulmonary hypertension, or
• difficult airway management.

Question 6

Would you perform an exchange transfusion?

(A 32-year-old, 99 kg, G4P3 female requires a repeat cesarean section due to severe preeclampsia. She is at 36 weeks gestation, with a history of three previous cesarean sections. The obstetrician informs you she does not know the patient and that there has been no prenatal care. She further reports shortness of breath with exertion and frequent hospital admissions due to pain from her sickle cell disease. Her surgical history consists of a splenectomy 18 years ago and retinal detachment surgery under local anesthesia 1 week ago. Her current medications include hydroxyurea and oxycodone. She reports taking narcotics routinely for the past couple of years and is afraid she is becoming addicted. Hgb = 7.8 g/dL. BP = 188/104 mmHg.)

Answer 6

For this moderate risk surgery, I would utilize a more conservative strategy of simple transfusion of leukocyte-reduced, hemoglobin S-free, red blood cells to achieve a hematocrit of 30%

(leukocyte reduction is important to reduce the risk of HLA alloimmunization, RBC alloimmunization, cytomegalovirus transmission, febrile non-hemolytic transfusion reactions, and immune suppression).

While this issue is controversial, there is evidence suggesting that this more conservative strategy is as effective in reducing the perioperative complications associated with sickle cell disease as are more aggressive strategies, such as exchange transfusion to reduce the HbS% to < 30-40%.

Moreover, there is some evidence that more aggressive strategies are associated with more transfusion-related complications.