Sickle Cell Disease

Epidemiology

  • xxxx

Physiology

  • xxxx

Clinical Presentations

Infectious Manifestations

  • Increased Risk for Infection with Encapsulated Organisms (see Bacteria and Fungi, [[Bacteria + Fungi]]): due to auto-splenectomy which commonly occurs due to recurrent splenic infarcts in childhood
    • Auto-splenectomy is so common that the presence of palpable splenomegaly after age 5 suggests the presence of a co-existent hemoglobinopathy (such as thalassemia or hemoglobin C)

Hematologic Manifestations

Pulmonary Manifestations

Acute Chest Syndrome

  • Epidemiology: occurs during a sickle cell vaso-occlusive crisis
  • Possible Etiologic Factors
    • Fat Embolism: due to diffuse bone marrow infarction
    • Diffuse Pulmonary Vaso-Occlusion: common
    • Fluid Overload: due to aggressive hydration or PRBC transfusion
    • Infection
  • Diagnosis
    • ABG: hypercapnia with respiratory acidosis was noted in 42% of acute chest syndrome cases in one series [MEDLINE]
    • CXR/Chest CT Patterns: alveolar infiltrates (may be diffuse)
    • Echocardiogram: left ventricular dysfunction is not commonly seen during crises
  • Clinical
    • Chest Pain (see Chest Pain , [[Chest Pain ]])
    • Cough (see Cough, [[Cough]])
    • Diffuse Bone Pain
    • Dyspnea (see Dyspnea, [[Dyspnea]])
    • Fever (see Fever, [[Fever]])
  • Prognosis: potentially life-threatening

Acute Chest Syndrome of Pregnancy

  • Physiology
  • Clinical

Sickle Cell Chronic Lung Disease (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]])

  • xxx

Sickle Cell-Associated Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

  • Epidemiology:
  • Predisposing Factors
    • Aseptic necrosis of bone
    • Previous episodes of acute chest syndrome (risk increases with number of previous episodes)
    • Patients with hemoglobin SC disease (Sickle C disease): may present with cor pulmonale without frequent antecedent acute chest syndrome episodes (due to higher Hct with increased blood viscosity -> increased sickling in precapillary pulmonary circulation)
  • Pulmonary hypertension has been described most frequently in patients with SCD with histologic lesions similar to those found in IPAH, including plexiform lesions in 1 case series
  • However, the prevalence of PAH in SCD is not clearly established.
  • The largest study of patients with SCD, which defined PH echocardiographically by the presence of tricuspid regurgitation jet velocity (TRV) greater than or equal to 2.5 m/s, found that 32% of patients had PH
  • However, using a TRV >2.5 m/s on echocardiography to define PH can lead to a substantial number of false positive cases of PH not confirmed by right heart catheterization
  • When a TRV >3.0 m/s was used, corresponding to an estimated systolic PAP of >41 mm Hg, only 9% of the cohort met the criteria for PH.
  • Right heart catheterization was carried out in only 18 of 63 patients with TRV >2.5 m/s. In this subpopulation, PH defined by a mean PAP >25 mm Hg was confirmed in 17 patients; however, pulmonary wedge pressure was elevated in some patients.
  • A substantial proportion of patients with SCD have pulmonary venous hypertension: 46% in 1 study of 26 patients with SCD and PH
  • In addition, some patients present with a hyperkinetic state with moderate elevation in mean PAP and normal PVR.
  • Thus, although it appears that some patients with SCD do develop PAH, the prevalence of PAH in SCD is undoubtedly much lower than 32%
  • Prospective epidemiologic studies using echocardiographic screening and direct hemodynamic confirmation with right heart catheterization in all patients with suspected PH are ongoing and will evaluate the precise prevalence of PAH in SCD.
  • The mechanism of PAH in SCD remains uncertain.
  • A probable hypothesis is that chronic hemolysis results in high rates of nitric oxide consumption and produces a state of resistance to nitric oxide bioactivity
  • Consequently, smooth muscle guanosine monophosphate, a potent vasodilator/antiproliferative mediator, is not activated

References

  • Microangiopathic hemolytic anemia and thrombocytopenia in primary pulmonary hypertension. N Engl J Med 1972;287:869–70
  • Pulmonary hypertension and right heart failure in patients with