Hematology Flashcards
How is cyclic neutropenia diagnosed? How long are cycles?
Diagnosis is made by obtaining serial neutrophil counts during a 2-3 month period
Cycles last an average of 21 days in 70% of patients
What are the clinical features of ITP?
Illness typically occurs 1-4 weeks after a viral infection
Begins abruptly with cutaneous bleeding or mucous membrane bleeding
Internal bleeding into the brain, kidneys, or GI tract may occur but is rare
In ITP, very low platelet counts (<20,000) or active bleeding warrant treatment with…
What is the second line agent?
IVIG or corticosteroids
Anti-D immunoglobulin is a second-line agent that may aslo be effective
What follow up is recommended beginning at 2 years of age for SS disease patients and why?
Serial transcranial Doppler ultrasound or magnetic resonance angiography to identify patients at risk for stroke
What is polycythemia vera?
A malignancy involving the RBC precursor that occurs during childhood
What is the most common cause of neutropenia during childhood?
Infections
What is deficient in scurvy?
Vitamin C
What is the management for hemophilia B (Christmas tree disease)?
Factor IX replacement
Why is ferritin not always a reliable marker of iron deficiency anemia?
Because ferritin is also an acute-phase reactant, it may be increased in infection, disease states, and stress
What is the genetic cause of Sickle cell (SS) disease?
SS disease is caused by a single amino acid substitution of valine for gluamic acid on position 6 of the ß-globin chain of Hgb
Mutation results in polymerization of Hgb within the RBC membrane when the RBC is exposed to low oxygen or acidosis
autosomal recessive
Why do thalessemias lead to increased size of bones in the face and skull?
Both types of thalassemia result in hemolysis that elads to increased bone marrow activity; as marrow activity increases, the marrow spaces enlarge, increasing the size of bones
What are red blood cell aplasias?
A group of congenital or acquired blood disorders characterized by anemia, reticulocytopenia, and a paucity of RBC precursors in the bone marrow
Describe autoimmune neutropenia and isoimmune neutropenia
Autoimmune: A disorder in which antineutrophil antibodies are produced in response to infection, drugs, SLE, and juvenile rheumatoid arthritis
Isoimmune: Passive transfer of antineutrophil antibodies from the mother to her fetus after maternal sensitization by antigens on the fetal neutrophils
What are some clinical manifestations of vitamin K deficiency?
- Bruising
- Oozing from skin puncture wounds
- Bleeding into organs
What are two inherited disorders involving factor VIII of the clotting cascade?
Hemophilia A and von Willebrand’s disease
What are some common causes of normocytic, normochromic anemias?
Hemolytic anemias,
red cell aplasias, and sickle cell anemia
Possible complications of polycythemia are…
Thrombosis and bleeding
What is DIC?
A group of laboratory and clinical features indicative of both accelerated fibrogenesis and fibrinolysis; the initiating event is clotting that leads to consumption of procoagulant factors and resultant hemorrhage
How is SS disease diagnosed?
Usually diagnosed at brth through state newborn screening programs; Hgb Electrophoresis is a highly sensitive and specific test
The Hgb is ______ at birth and reaches the physiologic lowest point between _ and _ months of age in the term infant (between _ and _ months in the preterm infant)
The Hgb is high at birth and reaches the physiologic lowest point between 3 and 4 months of age in the term infant (between 1 and 2 months in the preterm infant)
What laboratory findings are seen in DIC and liver disease?
- Prolonged PT and aPTT
- Thrombocytopenia
- Elevated fibrin degradation products
What is the management for DIC?
Therapy includes treatment of the underlying cause and transfusions of fibrinogen, FFP, and platelets as needed (same for liver disease); Heparin may be useful if underlying defect cannot be corrected
What is the difference between SS disease and SS trait?
SS disease: result of having 2 genes for Hgb S
SS trait: result of having only one gene for Hgb S; patients are usually asymptomatic without anemia
What are the clinical features of cyclic neutropenia?
Cyclic alterations in neutrophil counts results in regular episodes of neutropenia with resultant infections
Macrocytic (megaloblastic) anemias are characterized by MCV > __
What are the two major causes in children?
MCV?
95
Folic acid and Vitamin B12 deficiencies
MCV ( mean corpuscular volume) - average volume and size of individual erythrocytes.
What is the most common acquired platelet abnormality in childhood?
Immune thrombocytopenic purpura (ITP)
What causes the majority of iron deficiency anemia?
Inadequate iron intake
What are some clinical features of moderate anemia?
- Weakness and fatigue
- Decreased exercise tolerance
- Irritability
- Tachycardia
- Tachypnea
- Anorexia
- Systolic heart murumur
What is the most common hereditary bleeding disorder?
What is it’s inheritance pattern?
von Willebrand’s disease
Autosomal dominant
How are normocytic, normochromic anemias differentiated (name the lab and the significance of the lab values)?
Reticulocyte count
- Low reticuloyte count: Reflects bone marrow suppression or failure and is consistent with red cell aplsias, pancytopenia, and malignancy
- High reticulocyte count: reflects bone marrow production of RBCs as seen in hemolytic anemias and sickle cell anemia
What is Henoch-Schonlein purpura?
An IgA-mediated vasculitis that present with palpable purpura on the lower extremities and buttocks, renal insufficiency, arthritis, and abdominal pain; platelet count normal
How is a painful bone crisis managed?
- Pain control
- IV fluids at 1.5-2x maintenance
- Incentive spirometry to decrease risk of Acute chest syndrome
- May respond to partial exchange transfusion
What is the management for hemophilia A?
Treatment includes prevention of trauma and replacement of factor VIII
Desmopressin acetate (DDAVP) may cause the release of stored factor VIII from the patients
In what two age groups is iron deficiency most common? Why?
In infancy what is the cause?
9-24 months of age: owing to inadequate intake and inadequate iron stores
Adolescent girls: because of poor diet, rapid growth, and loss of iron in menstrual blood
infancy- microhemorrhages in the gut due to early intake of cows milk
What is the difference between hemophilia A and von Wilebrand’s disease?
Hemophilia A: Defect in factor VIII procoagulant activity; platelet function is normal
von Willebrand’s disease: Factor VIII procoagulant activity is variable but platelet function is defective because of a decrease or defect in vW factor which is necessary for platelet adhesion to blood vessel walls
What is the management for vitamin K deficiency?
- Administration of vitamin K
- Intramuscular administration of vitamin K after birth prevents hemorrhagic disease of the newborn
- FFP in severe disease
What types of occult blood loss can lead to iron deficiency anemia?
Secondary to polyps, Meckel’s diverticulum, IBD, PUD, and early digestion of whole cow’s milk (iron-poor) beore age 1
What is autoimmune hemolytic anemia (AIHA)?
Occurs when antibodies are misdirected against the RBCs
What is the major Hgb in RBCs? What is it made up of?
Hemoglobin A1; A tetramer of two α chains and two ß chians
In Rh hemolytic disease, what test is strongly positive?
Direct Coombs
When does Rh disease occur?
Rh hemolytic disese occurs when the mother (who has no Rh antigen) produces antibodies to the Rh antigen on her fetus’s RBCs; In subsequent pregnancies antibodies pass from the mother to the fetus causing hemolysis and hydrops fetalis
Mother is Rh negative and father is Rh Positive so thre is a chance baby can be Rh positive
mom is given Rhogam
What is thrombocytopenia?
Decreased number of platelets, generally < 100,000; most common cause of bleding
What aside from iron deficiency anemia, thalassemia and sideroblastic anemia can cause microcytic hypochromic anemia?
Lead toxicity and anemia of chronic disease
What is the management for polycythemia?
Treatment of underlying cause; phlebotomy is also used to keep Hct < 60%
What clotting factors require vitamin K?
Factors II, VII, IX, and X and proteins C and S
What percentage of ITP cases resolve spontaneously?
How long must ITP last before it is considered chronic ITP?
70-80% resolve spontaneously
Chronic ITP is diagnosed if ITP lasts > 6 months
What is seen on blood smear in ITP?
Few large “sticky” platelets
What can lead to folic acid deficiency?
- Diet lacking uncooked fresh fruits and vegetables
- Exclusive feedings with goat’s milk
- Decreased intestinal absorption due to celiac disease, enteritis, chron’s disease…
How is von Willebrand’s disease diagnosed?
- Prolonged bleeding time and aPTT may be present but not always
- Quantitative assay for vWf antigen and activity (ristocetin cofactor assay)
What are the two most common causes of microcytic hypochromic anemias during childhood?
Iron deficiency anemia and ß-thalassemia trait
- lead poisoning
What are the causes of ITP? Which is most common?
ITP may be viral, drug induced, or idiopathic (most common)
How do you treat ß-thalassemia minor?
What misdiagnosis can lead to harmful treatment of ß-thalassemia minor?
No treatment is required
Iron deficiency anemia (may be treated inappropriately with iron when iron level in ß-thalassemia minor is normal or elevated)
Why is the reticulocyte count helpful?
Reticulocyte count reflects the number of immature RBCs in circulation; Low reticulocyte counts indicate bone marrow failure or diminished hematopoiesis
What is ß-thalassemia major?
May be caused by either total absence of the ß-globin chains or deficient ß-globin chain production
What are the two types of AIHA?
- Primary: Generally idiopathic in which no underlying disease is identified; viral infections and drugs may be causal
- Secondary: associated with udnerlying disease process, such as lymphoma, SLE, or immunodeficiency disease
What type of bacteria are patients with SS at risk for? Why?
Infection is a result of decreased splenic function so patients are at risk for infection with encapsulated bacteria (Hib, Strep pneumo, Salmonella, N. meningitidis)
What can lead to vitamin K deficiency?
- Dietary deficiency if in early infancy
- Pancreatic insufficiency
- Biliary obstruction
- Prolonged diarrhea
- Medications
- Hemorrhagic disease of the newborn
How does ß-thalassemia lead to hemochromatosis? How can this be delayed?
Hemochromatosis is caused by increased iron absorption from the intestine and from iron transfused in transfused RBCs; Chelation of iron with deferoxamine promotes iron excretion and may help delay hemochromatosis
α-thalassemia is most common in…
ß-thalassemia is most common in
α-thalassemia: Southeast Asians
ß-thalassemia: Mediterranean background
What is the definition of anemia?
A reduction in RBC number or in hgb concentration to a level that is more than two standard deviations below the mean
In ABO hemolytic disease, what are the results and strength of a direct coombs test?
Weakly positive
What types of crieses occur in SS disease?
- Vasoocclusive crisis
- Painful bone crisis
- Acute abdominal crisis (sickling in mesenteric artery)
- Stroke
- Priapism
- Acute chest syndrome (pulmonary infiltrate)
- Sequestration crisis (accumulation of blood in spleen)
- Aplastic crisis (parvovirus B19 or other infection)
- Hyperhemolytic crisis
What are the clinical features of ß-thalassemia?
what will lab values show?
features of beta- thalassemia minor, and alpha - trait
- Hemolytic anemia beginning in infancy
- Hepatosplenomegaly
- Bone marrow hyperplasia (thalassemia facies), frontal bossing - due to the increases hematopoiesis
- Delayed growth and puberty may be present
- pale skin
- mild jaundice
decreased: HGB, MCV, (microcytic, hypochromic)
increase: reticulocyte count
Alphsa & minor - usually asymptomatic
What are the clinical features of von Wilebrand’s disease?
- Most patients have mild to moderate bleeding involving mucocutaneous surfaces
- Epistaxis, menorrhagia, bruising, and bleeding after dental extraction or tonsillectomy
- Hemarthroses are unusual
What is the most dreaded complication of hemophila A?
CNS bleeding (usually the result of head trauma)
What is started in SS disease patients within the first few months of life and why?
Daily oral penicillin prophylaxis to decrease the risk of S. pneumoniae infection
When are there clinical features of SS disease?
Not until after Hgb F declines (protective until 6 months of age)
What is the meaning of microcytic, hypochromic anemia?
Small, pale RBCs; low MCV
What is the leading cause of death from SS disease?
Infection
What are the absolute neutrophil counts for mild, moderate and severe neutropenia?
- Mild: ANC of 1,000-1,500
- Moderate: 500-1,000
- Severe: ANC < 500
What are the 3 categories of von Wilebrand’s disease?
- Type I (classic type): Mild quantitative deficiencies of vWf and factor VIII protein - Most common form
- Type II: Qualitative abnormalitiy in vWf
- Type III: Absence of vWf; the most severe type
What is the inheritance pattern of hemophilia A?
X-linked
What increases Hgb F and has been shown to decrease vasoocclusive crises in SS disease?
Hydroxyurea
What is seen on blood smear in SS disease?
Sickled cells, target cells, Howell-Jolly bodies
What are the laboratory findings of ß-thalassemia?
- Severe hypochromia and microcytosis, low MCV
- Target cells and poikilocytes
- Elevated unconjugated bilirubin, serum iron, and LDH
- increased reticulocyte count
What clinical features suggest abnormal hemostasis in children?
- Cutaneous bleeding (ecchymoses)
- Spontaneous epistaxis
- Prolonged bleeding after simple surgical procedures
- Recurrent hemarthroses
- Deep venous thrombosis
What lab findings are seen in hemophilia A?
- Prolonged aPTT
- Normal PT, bleeding time, platelet count, and platelet function assay
- Low factor VIII protein activity
What are the clinical features of fulminant acute type AIHA? In what population does this occur?
Preceded by respiratory infection; features include acute onset of pallor, jaundice, hemoglobinuria, and splenomegaly
Occurs in infants and young children; complete recovery is expected
What is passive autoimmune thrombocytopenia?
Occurs when the mother has ITP, and antibodies against her own platelets cross the placenta and destroy the fetus’s platelets
Which crises is treated with splenectomy?
Which are treated with supportive care and transfusion of RBCs?
Splenectomy: Sequestration crisis
Supportive care + RBCs: Aplastic crisis and hyperhemolytic crisis (rapid hemolysis)
What is polycythemia?
An increase in RBCs relative to total blood volume or hematocrit > 60%
What are the hallmark clinical features of Hemophila A? What are the features of severe, moderate, and mild forms of the disease?
- Hallmarks: Hemarthroses and deep soft tissue bleeding
- Severe: spontaneous bleeding
- Moderate: Bleeding only with trauma
- Mild: Bleeding only after surgery or major trauma
α-thalassemia results from…
ß-thalassemia results from…
Defective α-globin chain synthesis
Defective ß-globin chain synthesis
What is a major constitutent of Hgb during fetal and early postnatal life? When does it disappear?
Fetal hemoglobin (Hgb F); Disappears by 6-9 months of age
In management of iron deficiency anemia, iron is given with ______ to enhance intestinal absorption
Vitamin C (orange juice)
What is the management for von Wilebrand’s disease?
DDAVP - most useful in type I disease and is sometimes effective in type II disease
Cryoprecitpitate (contains intact vWf) - used for serious bleeding, extensive surgeries, or for type III disease
Name the RBC aplasia:
Anemia within the first year of life, rapid onset
One fourth to one third have physical findings: craniofacial, renal, cardiac anomalies
Short stature; triphalangeal thumbs
Diamond Blackfan anemia
What other disease associated with SS disease may mimic a painful bone crisis? What is the most common cause?
Osteomyelitis, most commonly caused by salmonella (although S. Aureus may also cause osteomylitis)
Describe the mechanism leading to increased tranferrin in iron deficiency anema?
Iron stores disappear first leading to low serum ferritin; As serum iron decreases iron binding capacity increases manifested as increased transferrin and decreased transferrin saturation
