sickle cell anemia Flashcards
what is hydroxyurea and how does it work?
treats SCA by increasing HbF and decreasing sickling. it increases HbF production by NO activation which upregulates cGMP. this in turn increases gamma globin synthesis and HbF production from F cells.
decreases sickling by reduced sickle adhesion to endothelium, improved SC hydration, NO-mediated vasodilation, and reduced neutrophil activation (which decreases the amount of pro-inflammatory mediators released)
where is the classic SCA mutation?
chromosome 11 resulting in substitution of valine for glutamic acid on the beta chains of Hb
what is the pathophysiology of SCA?
HbS molecules can polymerize into a sickled shape. these sickled polymers can cause occlusion of capillaries and ischemic end-organ injury. they are hemolyzed much faster than RBCs with Hb (HbS RBC lifespan: 12-17 days, Hb RBC lifespan: 120 days)
what circumstances increase sickling?
hypoxia (PO2
what is 2,3-DPG?
a molecule that preferentially binds to the beta subunit of deoxygenated Hb (more space for it to bind than with oxygenated Hb). it decreases the affinity of Hb to O2, thereby promoting the release of the remaining O2 molecules
if hypoxia is related to sickling, why don’t all HbS RBCs sickle in the presence of venous blood?
it is a time-dependent process. although some will start to sickle, only about 5% have sickled by the time they reach the lungs and then oxygenation results in a reversal of much of this.
what is aplastic crisis?
bone marrow suppression, usually secondary to infection (parvovirus B19) or folate deficiency. decrease in production coupled with decreased life span of HbS RBCs leads to profound anemia.
how is aplastic crisis treated?
correction of folate deficiency and blood transfusion until bone marrow suppression resolves (4-7 days)
what is the appropriate preop evaluation of this patient?
thorough history and physical.
given her history of SOB, i would be looking for history of aplastic crisis, acute chest syndrome, and any end-organ damage, such as cor pulmonale, CHF, MI, pulm fibrosis, or pulm HTN. on physical exam, i would specifically evaluate her airway for potential difficulty, IV sites for bleeding, recent BPs and also current volume status.
to aid in my evaluation of these problems i would order CXR, ECG, room air ABG, CBC (H/H and platelet count), and BMP (to check renal function). other tests might include ECHO and PFTs but these would be directed by her history and urgency of c-section.
given her severe anemia, preeclampsia, and her history of previous c-section x 3, a blood transfusion would be prudent and likely she may need IVF infusion (preeclampsia is associated with further hypovolemia).
is an exchange transfusion necessary?
likely no, a transfusion of leukocyte-reduced HbS-free RBCs to a Hct of 30% would be adequate. exchange transfusion is associated with many negative sequalae, such as electrolyte disturbances, thromboembolism, and thrombocytopenia.
would you do general or regional?
due to risk of difficult airway (edema secondary to preeclampsia) and increased risk of aspiration (secondary to pregnancy), i would prefer regional. i do recognize that she has thrombocytopenia and would need careful evaluation for possible decreased platelet function (IV site bleeding, easy bruising, etc)
epidural or spinal or cse?
i would prefer epidural. it can be slowly titrated to effect, which will give her more time to compensate for the sympathectomy than a spinal will. additionally, it is a repeat csection x 4 and the surgery may outlast the effect of the spinal. i would prefer to have an epidural to be able to give extra medication through the catheter if necessary. finally, with her chronic narcotic use, an epidural would be the best choice for controlling postop pain.
how can you reduce risk of sickling?
I would avoid hypotension and venostasis by ensuring adequate fluid administration to compensate for the sympathectomy from neuraxial anesthesia. I would avoid hypoxia by administering supplemental O2 and monitoring pulse-oximetry. I would ensure adequate oxygen-carrying capacity by preoperatively transfusing the patient to Hct of 30%. I would maintain normothermia (hyperthermia increases O2 consumption and hypothermia causes vasoconstriction). I would ensure adequate ventilation to avoid acidosis.
what is the diff dx of seizures immediately following delivery?
- amniotic fluid embolus
- eclampsia
- vaso-occlusive crisis
- local anesthetic toxicity
how will you manage this patient?
immediate cricoid pressure, supply 100% O2, stop all local anesthetics. call for help, difficult airway supplies, and lipid rescue kit. IV versed to treat seizure. perform careful laryngoscopy and secure airway.
once ett placement has been confirmed, i would reassess the patients vital signs, treating hemodynamic instability (with IVF and pressors) and ensuring adequate ventilation (elevated PCO2 lowers seizure threshold, increases sickling, prolongs LA toxicity) and oxygenation (hypoxia increases sickling, prolongs LA toxicity). ensure adequate IV access and place an intra-arterial catheter and check magnesium (as well as ensure t&c has been performed - may need blood products due to coagulopathy from AFE)).
