Sickle cell disease: Clinical sciences

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Introduction0:00–0:31

Sickle cell disease, or SCD for short, is a genetic disorder affecting hemoglobin that causes red blood cells to become deformed and sickle-shaped.
Sickled cells can obstruct small blood vessels and disrupt the supply of oxygen to tissues, resulting in severe pain and tissue damage within any organ system.
Once the diagnosis of SCD is confirmed, patients should be monitored for related complications.Now, if your patient presents with a chief concern suggesting SCD, you should first perform an ABCDE assessment to determine if your patient is unstable or stable.

Unstable patients0:31–1:30

If unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access, start IV fluids, and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry.
Finally, if needed, provide supplemental oxygen.Now, here’s a clinical pearl! Severe complications of SCD include acute chest syndrome and acute episodes of vaso-occlusion and hemolysis that present with life-threatening ischemia or infarction of the central nervous system or pulmonary vasculature.
Be on the lookout for the sudden development of red-flag signs such as new-onset weakness, altered mental status, chest pain, or respiratory distress.
Now, let’s go back to the ABCDE assessment and take a look at stable patients. First, obtain a focused history and physical examination.

Stable patients1:30–2:20

Your patient might report weakness and fatigue, as well as a history of chronic anemia and recurrent infections. Additionally, the family history may be significant for other relatives with SCD.
Patients often experience acute or chronic pain, especially in the long bones, pelvis, or back. On the other hand, a physical exam typically reveals an ill-appearing patient with tachycardia and an audible heart murmur on cardiac auscultation.
Skin exam commonly reveals jaundice and pallor, and you might also notice scleral icterus. Finally, you might find bone and joint tenderness, warmth, or swelling.At this point, you should suspect SCD, so order labs, including a CBC with a peripheral smear, a reticulocyte count, CMP, haptoglobin, and hemoglobin electrophoresis.

Suspect SCD2:20–2:32

SCD diagnosis2:32–3:38

Now, let’s take a look at the lab results. The CBC will demonstrate low hemoglobin and hematocrit, and the peripheral smear will reveal sickle-shaped cells.
There might be an elevated reticulocyte count, increased levels of indirect bilirubin, and high lactate dehydrogenase; while haptoglobin will be low, as these patients are actively hemolyzing.
Hemoglobin electrophoresis will reveal the presence of Hemoglobin S as well as absent or decreased Hemoglobin A levels. Based on these lab results, you can diagnose sickle cell disease.
Now, here’s another clinical pearl to keep in mind! All newborns in the US are screened for SCD.
In other words, most SCD diagnoses are established in early infancy. Infants with SCD are at increased risk of infection from encapsulated organisms, such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, so, in addition to routine childhood immunizations, they should receive prophylactic penicillin until 5 years of age.
Ok, now once you diagnose SCD, begin the initial steps of medical management. Patients with SCD commonly present with acute vaso-occlusive episodes, also known as pain crises, so it’s important to administer pain medication promptly.

Acute and Chronic Management3:38–5:08

If the pain isn’t severe you can start with NSAIDs. But, keep in mind that patients often require intravenous opioids for effective pain control, so consider patient-controlled analgesia for hospitalized patients.
Additionally, start IV fluids to ensure adequate hydration and reduce blood viscosity. Finally, if anemia is severe and symptomatic, give a transfusion of packed red blood cells.
Transfusions are beneficial acutely, for severe symptomatic anemia, as well as prophylactically, for stroke prevention. However, frequent transfusions can lead to alloimmunization and iron overload, so be cautious when deciding whether to transfuse your patient.Alright, now that you’ve provided initial treatment, it’s time to focus on chronic medical management.
This includes medications like hydroxyurea, which increases fetal hemoglobin production and reduces cell sickling, as well as folic acid, which is essential for adequate red blood cell production.
Individuals with sickle cell disease are at increased risk of infection, so make sure your patient is up to date on immunizations, especially those that protect against infections with encapsulated organisms like Streptococcus pneumoniae.
Finally, encourage genetic counseling for all first-degree relatives, in order to discuss inheritance of SCD as well as the risk of transmission to future children.

Related complications5:08–5:21

Alright, now once you initiate the management, make sure to assess your patient for complications related to SCD. First, let’s start with a stroke!

Stroke5:21–5:48

These patients could present with a headache or neurological symptoms, like unilateral weakness or speech difficulties, and the physical exam demonstrates focal neurological deficits like hemiparesis.
In this case, order a CT of the head, and if findings suggest ischemia or infarction, diagnose stroke. Next, let’s take a look at acute chest syndrome!

Acute chest syndrome5:48–6:36

These individuals might present with fever, cough with or without sputum production, shortness of breath, and chest pain.
Physical examination may reveal an elevated temperature and hypoxia, with decreased breath sounds and crackles on auscultation.
Next, order a chest X-ray, and if it shows pulmonary infiltrates, atelectasis, cardiomegaly, or effusion, diagnose acute chest syndrome.
Here’s a clinical pearl! Patients with acute chest syndrome are often unstable and may develop respiratory failure, requiring ICU admission and even early exchange transfusion to decrease the hemoglobin S to less than 30% of total hemoglobin.Switching gears and moving on to avascular necrosis of the femoral head.

Avascular necrosis of femoral head6:36–7:16

History findings include pain in the hip, groin, or buttock, as well as reduced mobility. Physical exam often shows a limited range of hip motion with gait changes, and there could even be muscle wasting and crepitus.
Next, order an X-ray or MRI of the hips, and if imaging reveals sclerosis or a flattened or collapsed femoral head, diagnose avascular necrosis of the femoral head.Now, if your patient has a history of recurrent or severe infections, especially with encapsulated organisms like Streptococcus pneumoniae, review the peripheral blood smear.

Functional asplenia7:16–8:28

If you find Howell-Jolly bodies within the red blood cells, diagnose functional asplenia. Now, here’s a high-yield fact!
While most adults with SCD acquire functional asplenia as a consequence of surgical splenectomy or splenic auto-infarction, young children usually still have intact spleen function.
This predisposes children to splenic sequestration, a condition in which blood elements become trapped in the spleen, which can eventually result in massive splenomegaly, anemia, and thrombocytopenia.
In this case, treatment includes urgent transfusion, and, if sequestration recurs, surgical consultation for splenectomy.
Another unique complication of SCD in young children is dactylitis, a condition in which acute vaso-occlusion of the fingers and toes leads to redness, swelling, and pain, also known as sausage digits.
Just as in other vaso-occlusive crises, dactylitis should be treated with pain control and fluids.Ok, next up is priapism.

Priapism8:28–8:53

These patients report a painful, prolonged erection, and physical examination confirms a persistent erection. In this scenario, order an emergent penile ultrasound, and if it shows decreased cavernosal arterial flow, diagnose priapism.
Now, let’s say a patient presents with upper abdominal pain, which may occur with nausea and vomiting, and a physical exam reveals right upper quadrant tenderness.

Gallstones8:53–9:29

Next, order an ultrasound, and if there’s a calculus within the gallbladder or common bile duct, you can diagnose gallstones.
Moreover, since SCD is a type of hemolytic anemia, chronic red blood cell destruction leads to persistently elevated unconjugated bilirubin levels.
This is the reason why these patients usually develop pigment gallstones.Another important complication related to SCD is retinopathy!

Retinopathy9:29–9:59

In this case, your patient will report impaired vision, and physical examination will confirm decreased visual acuity and restricted visual fields.
Fundoscopic exam might also reveal proliferative changes, neovascularization, and vitreous hemorrhage. These findings are highly suggestive of retinopathy.Finally, your patient might report painful sores on the lower legs, with the physical examination revealing ulcerated lesions of the legs, with surrounding hyperpigmentation.

Leg ulcers9:59–10:33

Additionally, you might notice signs of cellulitis, like local tenderness and redness, as well as lymph node enlargement.
In this case, you can make the diagnosis of leg ulcers.Here’s a clinical pearl! Leg ulcers in patients with SCD are often associated with DVT, so be sure to also obtain a lower extremity Doppler.Wrapping up,if your patient with SCD presents with any of these complications, be sure to provide management tailored to the specific complication, and continue ongoing chronic SCD treatments.Alright, as a quick recap...

Management10:33–10:50

If you suspect SCD, order labs, including CBC with peripheral blood smear, reticulocyte count, CMP, haptoglobin, and hemoglobin electrophoresis.

Review10:50–11:58

The CBC will reveal low hemoglobin and hematocrit, and the peripheral smear will reveal sickle-shaped cells. The reticulocyte count, indirect bilirubin, and lactate dehydrogenase are typically elevated; while haptoglobin is low.
Additionally, hemoglobin electrophoresis will reveal the presence of Hemoglobin S and the absence or reduction of Hemoglobin A levels.
Based on these findings, diagnose sickle cell disease. Next, provide acute medical management with pain control, hydration, and packed red blood cell transfusion, if needed.
Also, don’t forget to start chronic management with hydroxyurea, folic acid, regular immunization, and genetic counseling to first-degree family members.
Finally, assess all patients for complications, such as stroke, acute chest syndrome, avascular necrosis of the femoral head, functional asplenia, priapism, gallstones, retinopathy, and leg ulcers.