1. Pregnancy and SCD

2. Preconception
Hydroxyurea is teratogenic; pregnancy category class D medication.
Iron overload should treated before becoming pregnant
Chelation therapy should cease upon conception.
All patients should be started on 5 mg/day of folic acid
Individuals with chronic hemolysis may require a higher dose.

3. Ante-partum care Alloimmunization Thromboembolism
Evaluated during the first visit, at which time the risk of alloimmunization is high
Re-evaluated at weeks 24–28, and during delivery, if negative at the first visit
Thromboembolism
All hospitalized patients for an acute medical condition require thromboembolism prophylaxis with low molecular-weight or fractionated heparin, unless such treatment is contra-indicated

4. Ante-partum care Preeclampsia
Low-dose aspirin after 12 weeks' gestation may decrease the risk of preeclampsia, preterm birth, and poor pregnancy outcomes; however increase bleeding and placental abruption.

5. Ante-partum care: Transfusion in pregnancy
There is no consensus on transfusions in pregnancy.
In a meta-analysis of 1291 patients: Blood 2015;126:2424–2435
Prophylactic transfusions decreased maternal mortality (odds ratio [OR] 0.23)
Vaso-occlusive pain episodes (OR 0.26)
Pulmonary embolism (OR 0.07)
Perinatal mortality (OR 0.43)
Neonatal death (OR 0.2), and preterm birth (OR 0.59)
Low event rates & a variety of transfusion goals

6. Ante-partum care: Transfusion in pregnancy
Only RCT; prophylactic vs on-demand transfusions: N Engl J Med 1988;319:1447–1452
Lower vaso-occlusive pain crises (relative risk 0.28)
No significant difference in perinatal mortality, intrauterine fetal demise, or neonatal death
Study was underpowered and the rate of events was small.

7. Ante-partum care: Transfusion in pregnancy
Reasonable approach
Prophylactic exchange transfusions, especially in the third trimester, every 3–4 weeks
Chronic organ dysfunction
“History” of acute chest syndrome
Frequent pain crises
A goal hemoglobin of 10 g/dL and HbS <30%

8. Intra-partum Delivery is recommended at gestational weeks 38–40
The general medical indications for cesarean section patients are valid in those with SCD
Local-regional anesthesia preferred because it decreases the risk of sickling complications.
If patients undergo cesarean section they should be transfused to a goal hemoglobin of 10 g/dL.

9. Intra-partum
Thromboprophylaxis is recommended - low-molecular-weight heparin, or heparin.
LMWH/heparin should be discontinued 24 hr prior to delivery and recommenced 12 h thereafter.

10. Post-partum
Prophylaxis with LMWH/heparin should be maintained to 6 weeks after cesarean section.
Hydroxyurea should not be used during lactation as the drug passes into breast milk

11. Perioperative management in SCD

12. Preoperative transfusion
Cooperative Study of Sickle Cell Diseases. Blood. 1995;86(10):
In 717 patients undergoing surgical procedures
The combined incidence of all sickle cell-related complications postoperatively was significantly lower in those who had preoperative transfusion compared to those who did not have transfusion.
Similar results were demonstrated in individuals with sickle hemoglobin C (HbSC) disease

13. Preoperative transfusion
A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group. N Engl J Med ;333(4):
Compared the use of simple transfusion with a hemoglobin (Hb) goal of 10 g/dL preoperatively to the use of exchange transfusion to bring the HbS ≤30 percent.
No statistically significant reduction in the incidence of perioperative complications was seen between the two arms of the study

14. Preoperative transfusion
The transfusion alternatives preoperatively in sickle cell disease (TAPS) study: a randomised, controlled, multicentre clinical trial. Lancet. 2013;381(9870):930-8.
Randomized to either no preoperative transfusion or preoperative transfusion
Patients undergoing low risk (e.g., adenoidectomy, inguinal hernia repair)
Medium-risk (e.g., cholecystectomy, joint replacement) procedures
The transfusion goal was to raise the hemoglobin to 10.0 g/dL.
In patients with preoperative hemoglobin levels of 9.0 g/dL or higher, a partial exchange transfusion was done.
The study was closed early due to significantly more complications in the medium-risk, no preoperative transfusion arm than in the medium-risk transfusion arm (10/33 vs. 1/34).

15. Preoperative transfusion
2014 NIH Expert Panel Report
Strong Recommendation, Moderate-Quality Evidence
Transfuse RBCs to bring the hemoglobin level to 10 g/dL prior to undergoing a surgical procedure involving general anesthesia.

16. Stroke management in SCD

17. Hemorrhagic stroke most frequent in the 20- to 29-year age group.
HbSS have a high prevalence (4.01%) and incidence (0.61 per 100 patient years) of cerebrovascular accidents
Ischemic strokes have a bimodal distribution, being more common in children and older adults, and lowest in adults aged 20 to 29 years
Risk factors: prior TIA, low steady-state hemoglobin, recent episode of acute chest syndrome (ACS), and elevated systolic blood pressure
Hemorrhagic stroke most frequent in the 20- to 29-year age group.
Risk factors: low steady-state Hb and high leukocyte count

18. Acute focal neurologic deficits differential diagnosis
Acute arterial stroke (ischemic infarct)
Typically obtain an MRI of the brain to distinguish between a stroke and a TIA
Stroke: strong consideration is given for lifelong regular transfusion therapy
TIA: regular blood transfusion therapy only in the presence of other risk factors
Prior TIAs
Abnormal transcranial Doppler ultrasound measurements
Cerebral vasculopathy
Presence of silent cerebral infarcts

19. Acute focal neurologic deficits differential diagnosis
Hemorrhagic stroke
Most common neurologic event in adults with SCD
No etiology for hemorrhagic stroke is identified in most cases
Subarachnoid hemorrhage is the most common etiology
Intracranial aneurysm
No evidence-based approach
Seizures
Hemiplegic migraine

20. Acute focal neurologic deficits differential diagnosis
Posterior reversible encephalopathy syndrome (PRES)
Headache, seizure, visual disorders, and AMS, and supported by imaging findings that show parietal and occipital involvement of the brain, likely resulting from vasogenic edema
Can be associated with ACS
Central sinus venous thrombosis (CSVT)
MRV is the preferred initial imaging

21. Acute care Labs Imaging CBC, reticulocyte count
Type and cross match, HbS%
Prothrombin time, activated partial thromboplastin time
Basic metabolic profile
Imaging
MRI/MRV preferred (to evaluate for CSVT)
MRI preferred over a brain CT to detect both hemorrhage and cerebral infarct

22. Acute care Emergent exchange blood transfusion therapy preferred
Or simple transfusion, followed by exchanged transfusion
Subacute care
Repeat the MRI of the brain within 14 to 30 days after initial stroke

23. Long-term care Secondary prevention
Exchange transfusion preferred (less iron load)
Hydroxyurea
Hematopoietic stem cell transplant (HSCT) for secondary stroke prevention
May be best option in children