RBC Basics
What is the predominant hemoglobin at birth?
Fetal Hemoglobin (HbF)
HbF accounts for 90% of the circulating Hgb in a fetus at 24 weeks gestation, after which it aging to be replaced by adult Hgb. At birth, 50-80% of total Hgb is HbF
What is one of the first symptoms in infants and toddlers with sickle cell disease?
Sickle cell dactylitis
The first pain crisis in 1/3 of children with SCD. Symmetric painful swelling of hands and feet.
A 13 month-old boy has had several repeat CBCs since 8 months of age that have shown a WBC count 2,400-3,000 and an ANC <400. Recent bone marrow aspirate shows normocellular marrow with normal trilineage hematopoiesis.
What is the most likely diagnosis?
Chronic benign neutropenia
Most common cause of neutropenia in healthy children, thought to be caused by autoantibodies to granulocytes. Clinical diagnosis usually made around 8-11 months. Typically lasts ~2 years. Does not usually require treatment and there is no increased risk for infection.
4 year-old girls presents with acute onset bloody nose and petechial rash with purpura. Had a cold 2 weeks ago. Hemoglobin is normal, platelet count is 4,000. Peripheral smear is normal except for the lack of platelets and the ones that are seen are large (but not giant).
What is the most likely diagnosis?
Immune thrombocytopenia (ITP)
Caused by immune-mediated destruction of circulating platelets.
What is the factor deficiency in Hemophilia A? Hemophilia B?
Hemophilia A - Factor 8 deficiency
Hemophilia B - Factor 9 deficiency
Both are x-linked recessive, usually males, family history in males on the maternal side. Risk of bleeding correlates with severity of deficiency.
What is the lifespan of a mature RBC?
120 days
9 month-old presents with pallor, irritability, poor growth, hepatosplenomegaly, jaundice
Hemoglobin electrophoresis shows F only
What is the diagnosis?
B-thalassemia major
No B-globin production. Expansion of the bone marrow space in facial bones leads to facial changes. Hb F only is shown because there is no B-globin production to make HbA. Patients are typically transfusion dependent and often develop iron overload, requiring chelation.
4 year-old girl presents with fever, oral ulcers, cervical lymphadenitis, occasional rectal ulcers and neutropenia. These signs and symptoms occur about every 21 days.
What is the most likely diagnosis?
In the majority of patients, caused by an autosomal dominant mutation in ELANE gene. Causes 3-7 day periods of neutropenia about every 21 days. Granulocyte colony-stimulating factor and antibiotics given for infections.
13 year-old presents with bruises over legs, torso and head. URI 2 weeks ago and had a brief nosebleed 3 days ago. CBC is normal except platelet count of 3,000. Remainder of exam is normal, he plays no contact sports and has no active bleeding.
What is the next step in management
Close observation
Decision to treat based on severity of bleeding symptoms. No-mild bleeding can observe. More severe bleeding, treatment includes steroids, IVIG, or anti-Rh Ig.
A patient has preop labs done before T&A. He had a recent URI. aPTT is prolonged, PT and platelet count are normal. You perform a mixing study, mixing the patient's plasma 1:1 with normal plasma. The aPTT of the mixed plasma is normal.
Based on this, is the patient at risk for bleeding?
Yes
If aPTT normalizes with mixing study, suspect a clotting factor deficiency, which increases risk for bleeding
If aPTT does not normalize with mixing study, the patient has developed an inhibitor to a clotting factor protein, usually lupus anticoagulant (transient often after viral illness). This prolongs the aPTT but does not cause bleeding
What is the first site of RBC formation in the fetus?
Yolk sac
Begins at 2-3 weeks gestation. By 5-6 weeks gestation it shifts to the liver
Bone marrow takes over by 7 months gestation.
A 7-month old presents with pallor, poor feeding and growth failure. Laboratory evaluation shows normal white blood cell count and platelet count, and a microcytic anemia with reticulocytopenia. Physical exam shows cleft palate, heart murmur and absent thumbs.
What is the most likely diagnosis?
Diamond-Blackfan anemia
Typically present with severe anemia in the first year of life. About half have physical anomalies.
Other physical anomalies include microcephaly, short stature, low frontal hairline, hypertelorism, ptosis, broad flat nasal bridge, small/low-set ears, icrognathia, cleft palate, webbed neck, abnormal scapula, malformed/absent rhumbs, cataracts, congenital heart disease, hypospadias.
Patients with cyclic neutropenia are at increased risk for what type of infection?
Sepsis from Clostridium septicum
What syndrome presents with these findings
- autosomal recessive inheritance
- presents in the neonatal period with bleeding
- severe isolated thrombocytopenia
- decreased or absent megakaryocytes in the bone marrow
- absent radii but normal thumbs
Thrombocytopenia-absent radius (TAR) syndrome
Other congenital anomalies may be present such as congenital heart defects and other abnormalities of the extremities (hypoplastic carpals/phalanges, syndactyly, hip dysplasia, foot deformities) but the thumbs are present and normal!
14 year-old girl presents with heavy menstrual flow with her first menses. You do labs: PT/aPTT are normal. Factor 8 is low, vWF antigen is low, ristocetin cofactor activity is low.
What is the most likely diagnosis?
von Willebrand disease type 1
Most common of the 3 forms, is due to a decreased in amount of vWF. vWF helps platelets stick to exposed endothelium and other platelets and is also the carrier for factor 8. Factor 8 may be low-normal to moderately low because of its short half life when not bound to vWF. Ristocetin cofactor activity is a functional assay of vWF.
How much does a red blood cell transfusion of 10 cc/kg raise hemoglobin
2.5-3.0 g/dL
In RBC transfusion, pRBS are the primary product used (whole blood is rarely used). A unit is typically a total volume of 250-350 cc of pRBCs reconstituted in plasma
What congenital hereditary anemia has these characteristics?
- structural or functional abnormality of cytoskeleton proteins: spectrin, ankyrin and less commonly band 3 or protein 4.3
- complications can include cholelithiasis due to bilirubin stones and aplastic crisis from parvovirus
- a positive osmotic fragility test confirms the diagnosis
Hereditary spherocytosis
Autosomal dominant anemia. it is the most common congenital hemolytic anemia in population of northern European origin
What syndrome has these characteristics?
- White cell disorder with multiple modes of inheritance depending on the gene affected
- Multiple admissions at a young age with severe bacterial infection
- Absolute neutrophil count <200
- Bone marrow shows an arrest of neutrophils lineage maturation at the promyelocytic stage
Severe congenital neutropenia (AKA Kostmann syndrome)
Patient also have monocytosis and eosinophilia. Hish risk of severe bacterial infections and early death. Management G-CSF, BMT is curative.
What syndrome presents with these characteristics?
- severe throbocytopenia
- small platelets
- eczema
- immunodeficiency
- X-linked
Wiskott-Aldrich syndrome
Defect in actin cytoskeleton remodeling and cell polarization. Classical WAS is an immunodeficiency syndrome with T-cell dysfunction, autoimmunity, eczema, and an increased risk of hematologic malignancies.
Which of the following clotting factors is most likely to continue to be synthesized in the face of acute liver failure?
Prothrombin
Factor 8
Fibrinogen
Factor 7
Factor 8
Nearly all clotting factors are synthesized in the liver and will be affected with severe liver disease.
3 exceptions: tissue factor (many cell types), vWF (endothelial cells, megakaryocytes) and Factor 8 (endothelial cells)
What organ produces erythropoietin in the fetus?
Liver
Kidneys take over after birth
9 year-old presents with a history of short stature, absent thumbs, abnormal radii, microcephaly, café au last sports, dark pigmentation and renal anomalies. Today he presents with pallor, fatigue, bruising and petechiae. Blood counts show pancytopenia.
What is the most likely diagnosis?
Fanconi anemia
Autosomal recessive disorder involving poor DNA repair mechanisms. Presents with pancytopenia at a mean age of 8-9 years. Often have congenital anomalies but are not required for the diagnosis. Usually a microcytic anemia with or without other cytopenias, although usually become symptomatic after the development of other cytopenias.
3-year-old boy whose medical history is remarkable for multiple episodes of otitis media for the last 2 years and 2 episodes of pneumonia, one of which resulted in hospitalization for treatment with parenteral antibiotics. His parents report that he often has oily, foul-smelling stools, although his diet is similar to that of his siblings who have normal stools. He is below the third percentile for both weight and height. Labs show neutropenia.
What is the most likely diagnosis
Shwachman-Diamond Syndrome
CF symptoms +neutropenia. Sweat test is negative. Patients can also have skeletal abnormalities, particularly metaphyseal dysostoses. Supportive care with pancreatic enzymes. Depending on severity of infections, G-CSF or BMT. Predisposition to MDS and AML.
What syndrome presents with these findings?
- autosomal recessive inheritance
- Macrothrombocytopenia with giant platelets
- the platelets do not aggregate to ristocetin but do aggregate in response to adenosine diphosphate, epinephrine and collagen
Bernard-Soulier syndrome
Patients have a deficiency in glycoprotein 1b in the platelet membrane and results in inability to aggregate properly. Severe mucocutaneous bleeding starting in infancy. DDAVP (Desmopressin) can shorten the bleeding time in BSS. Recombinant activated factor VII (rFVIIa) has been used, often for bleeding that is unresponsive to DDAVP and/or platelet transfusions
3 year-old boy is in the PICU for extensive burns after pulling a pot of boiling water off the stove. He received fluid resuscitation. The nurse notices purple lesions below the level of the burns. CBC shows WBC 12,000, Hgb 10.2, platelets 32,000.
Describe the patient's PT, PTT and fibrinogen
Increased PT and PTT. Decreased fibrinogen
DIC secondary to extensive burns, presents with thrombocytopenia and purpura. Endothelial damage > tissue factor production > rapid consumption of coagulation factors and platelets > bleeding and end-organ damage