The following article covers most of the important points about Hereditary spherocytosis (HS) that are tested in the USMLE exam. Pay close attention to bold phrases as they are key points that appear in the exam as questions/hints.
HS is a common inherited
hemolytic anemia resulting from abnormalities in the proteins of the red
blood cell (RBC) membrane (mainly spectrin but also ankyrin, protein 4.2, and band 3).
It is usually inherited in an autosomal dominant pattern, is most
common in whites of Northern European descent, and is infrequent in
African Americans. (Hereditary elliptocytosis (HE) is another disorder of
the red cell membrane that is a common cause of inherited hemolytic
anemia in African Americans.)
The membrane abnormalities of HS
cause fragility of the red cell membrane with loss of surface area and a
resultant spheroid shape instead of the normal biconcave appearance.
The MCV is usually within the normal range for age, but may be slightly
elevated if there is a brisk reticulocytosis. MCHC is high due to the
relative cellular dehydration.
The abnormal RBCs become trapped in the
spleen where they are eventually hemolyzed (so-called extravascular
hemolysis).
This leads to an increase in LDH, unconjugated bilirubin.
Haptoglobin is a scavenger hor free
hemoglobin and is normal or decreased in HS (as the hemolysis is extravascular).
Osmotic fragility is increased in HS.
Splenectomy is a common treatment but should be delayed until after school going age, if possible, due to the risk of pneumococcal sepsis.
Penicillin prophylaxis is recommended for at least the first 5 years
after splenectomy with some doctors recommending treatment for life.
Showing posts with label HemeOnc. Show all posts
Showing posts with label HemeOnc. Show all posts
Key points to remember about sideroblastic anemia for the USMLE
-Sideroblastic anemia results from hereditary (X-linked) or acquired disorder of heme synthesis.
-It is a microcytic hypochromic anemia with a high RDW (red cell distribution width) Same as iron deficiency anemia.
-Iron studies will distinguish the two. In sideroblastic anemia serum iron, serum ferritin and transferrin saturation are increased.
-Severity can be mild or severe enough to need frequent transfusions.
-Treatment: Pyridoxine helps in some rare inherited cases but manu need periodic transfusions. Stem cell transplantation has been used to treat children who are dependent on blood transfusion.
Lead screening, levels and treatment in children
Current guidelines state that health-care professionals should use blood lead tests to screen children at ages 1 and 2 years. Older children should be screened in certain high risk situations.
The American Academy of Pediatrics policy statement recommends the use of venous samples for initial screening whenever possible. If capillary testing is performed and the lead concentration is greater than 10 mcg/dL, the lead concentration must be confirmed by a venous sample because capillary sampling is more likely to yield false-positive results due to contamination from skin.
Chelation therapy should be considered if lead concentrations are higher than 44 mcg/dL. The role of chelation is not clearly defined for children whose blood lead concentrations range from 20 to 45 mcg/dL. Levels below 20 mcg/dL can be monitored periodically.
Succimer is the drug of choice for children whose blood lead concentrations are > 45 mcg/dL. For levels >70 mcg/dL calcium-disodium EDTA can be added. The first dose always is succimer, followed 4 hours later by EDTA, because EDTA when given alone can worsen lead encephalopathy.
Types of Vitamin K
Three forms of vitamin K are known to humans as follows:
K1: Phylloquinone: It is the 'plant' form and is found in green leafy vegetables, vegetable oils, and dairy products. This is the form given to newborns as water soluble IM injection at birth.
K2: Menaquinone: It is the form manufactured by bacteria in the intestines.
K3: Menadione: This is artificially designed vitamin K that is not used any more because of its adverse effects (hemolysis).
Vitamin K is required for gamma carboxylation of GLU residues on coagulation factors (Factors II, VII, IX, and X are called vitamin K dependent factors). In absence of vitamin K abnormal/defunct proteins called PIVKAs (proteins induced by vitamin K absence) are formed. These cannot participate in the coagulation cascade leading to failure of clotting and bleeding.
Hemorrhagic Disease of the Newborn
Three forms of hemorrhagic disease of the newborn are recognized. The phrase is a misnomer because these can be seen during infancy after the neonatal period.
1) Early-onset: Typically presents during first 24 hours after birth and is seen in infants born to mothers who are deficient in vitamin K (those who are on seizure or tuberculosis medications). Site of bleeding is variable and can be serious (intracranial).
2) Classic: Presents between day 1 to 7 of life and is secondary to failure of administration of vitamin K at birth. Site of bleeding can be umbilicus, GI, skin, circumcision. Intracranial bleeding is less common.
3) Late: Presents from 2 weeks up to 6 months (rarely later) and is seen in exclusively or predominantly breastfed infants who did not get vitamin K at birth. Most common presentation is intracranial hemorrhage.
Treatment: Symptomatic (transfusion, supportive care, site specific treatment), FFP for active bleeding, vitamin K administration.
1) Early-onset: Typically presents during first 24 hours after birth and is seen in infants born to mothers who are deficient in vitamin K (those who are on seizure or tuberculosis medications). Site of bleeding is variable and can be serious (intracranial).
2) Classic: Presents between day 1 to 7 of life and is secondary to failure of administration of vitamin K at birth. Site of bleeding can be umbilicus, GI, skin, circumcision. Intracranial bleeding is less common.
3) Late: Presents from 2 weeks up to 6 months (rarely later) and is seen in exclusively or predominantly breastfed infants who did not get vitamin K at birth. Most common presentation is intracranial hemorrhage.
Treatment: Symptomatic (transfusion, supportive care, site specific treatment), FFP for active bleeding, vitamin K administration.
U.S. Preventive Services Task Force (USPSTF) recommendationson mammography
In November 2009, the U.S. Preventive Services Task Force (USPSTF) came out with new recommendations for routine mammography screening for woman aged 40 to 49 years. These are as follows:
-No routine screening mammography in women aged 40 to 49 years. The decision to start regular screening mammography before the age of 50 years should be an individualized one.
-The USPSTF recommends biennial (once every 2 years) screening mammography for women between the ages of 50 and 74 years
-The evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older.
-The evidence is insufficient to assess the additional benefits and harms of clinical breast examination beyond screening mammography in women 40 years or older.
-The USPSTF recommends against clinicians teaching women how to perform breast self-examination.
-The USPSTF concludes that the current evidence is insufficient to assess additional benefits and harms of either digital mammography or magnetic resonance imaging instead of film mammography as screening modalities for breast cancer.
Breast cancer, HER2 receptors and Monoclonal antibodies
One thirds of all breast malignancies have amplification of the HER2 gene. HER2 stands for human epidermal receptor type 2. HER2 receptor is a transmembrane tyrosine kinase receptor whose stimulation leads to a number of molecular pathways associated with tumor growth and progression.
Cancers that express HER2 have poorer prognosis.
Trastuzumab also known as Herceptin is a recombinant monoclonal antibody specifically directed against the HER2 receptor and it has been shown to be improve the response rate in breast cancer patients. This antibody is used in combination with chemotherapy including doxorubicin, cyclophosphamide and paclitaxel.
Another antibody named Lapatinib (a.k.a. Tykerb) which is a 4-anililoquinazoline kinase that inhibits the tyrosine kinase domains of HER2 receptor is also being studied.
National Comprehensive Cancer Network recommends use of these agents in addition to chemotherapy for patients with HER2-positive breast cancers that are larger than 1 cm and have spread to lymphnodes.
***This topic is hot for the USMLE***
Cancers that express HER2 have poorer prognosis.
Trastuzumab also known as Herceptin is a recombinant monoclonal antibody specifically directed against the HER2 receptor and it has been shown to be improve the response rate in breast cancer patients. This antibody is used in combination with chemotherapy including doxorubicin, cyclophosphamide and paclitaxel.
Another antibody named Lapatinib (a.k.a. Tykerb) which is a 4-anililoquinazoline kinase that inhibits the tyrosine kinase domains of HER2 receptor is also being studied.
National Comprehensive Cancer Network recommends use of these agents in addition to chemotherapy for patients with HER2-positive breast cancers that are larger than 1 cm and have spread to lymphnodes.
***This topic is hot for the USMLE***
Vitamin K and Coagulation - High yield facts
Vitamin K is a fat soluble vitamin needed for the gamma-carboxylation of clotting factors 2, 7, 9 and 10. Remember II VII IX and X
Initially PT is prolonged. PTT can be prolonged later on.
Clinical situations where vitamin deficiency can be seen:
-Newborns who did not receive Vit K at birth. (Breast milk has low levels of vit K).
-Patient on broad spectrum antibiotics (Because gut flora is disturbed. Normally the intestinal bacteria make a significant portion of our Vit K)
-Fat malabsorption syndromes. Vit K is a fat soluble vitamin hence it will go down the drain with the fat.
Management of Vit K deficiency:
-For acute bleeding give FFP (fresh frozen plasma)
-Vitamin K is available as injection and orally
Initially PT is prolonged. PTT can be prolonged later on.
Clinical situations where vitamin deficiency can be seen:
-Newborns who did not receive Vit K at birth. (Breast milk has low levels of vit K).
-Patient on broad spectrum antibiotics (Because gut flora is disturbed. Normally the intestinal bacteria make a significant portion of our Vit K)
-Fat malabsorption syndromes. Vit K is a fat soluble vitamin hence it will go down the drain with the fat.
Management of Vit K deficiency:
-For acute bleeding give FFP (fresh frozen plasma)
-Vitamin K is available as injection and orally
Treatment of von Willebrand's Disease
Desmopressin (1-deamine-8-D-arginine vasopressin [DDAVP]) is the mainstay of therapy for most patients with mild von Willebrand disease. DDAVP causes a 2-4-fold increase in plasma von Willebrand factor and FVIII concentrations in healthy responsive individuals.
DDAVP can be used to treat bleeding complications or to prepare patients with von Willebrand disease for surgery.
In type IIB von Willebrand disease, DDAVP may cause a paradoxical drop in the platelet count and should not be used without prior testing.
DDAVP can be used to treat bleeding complications or to prepare patients with von Willebrand disease for surgery.
In type IIB von Willebrand disease, DDAVP may cause a paradoxical drop in the platelet count and should not be used without prior testing.
Common paraneoplastic syndromes
Paraneoplastic Limbic Encephalitis :
PLE is characterized by irritability, seizures, short-term memory loss and depression. MRI reveals bilateral mesial temporal lobe hyperintensities on T2 weighted images. Small cell lung carcinoma is the most common associated cancer.
Paraneoplastic Cerebellar Degeneration :
PCD patients present with cerebellar signs. MRI may be normal in initial stages. Common malignancies associated with this syndrome include -Small cell lung cancer, ovarian cancer, breast cancer and Hodgkin's lymphoma.
Paraneoplastic Encephalomyelitis :
In this condition there is patchy inflammation involving multiple areas of the nervous system. The tumor most frequently involved is again Small Cell Lung Carcinoma.
Paraneoplastic Sensory Neuropathy :
It is usually sensory neuropathy.
Opsoclonus-myoclonus :
This syndrome usually affects young children. While 50% of children with this syndrome have neuroblastoma only about 2% of children with this tumor develop opsoclonus.
Lambert-Eaton Myasthenic Syndrome (LEMS):
This is a Neuromuscular junction disorder characterized by Acetylcholine release problems from the presynaptic terminal.Symptoms are similar to myasthenia gravis. Diagnosis is often made using EMG. LEMS results from immunologic attack against the presynaptic terminal that cause interference with the release of Acetylcholine.
The Indirect Coombs Test or Indirect Antiglobulin Test
Indirect Coombs test (also known as the indirect antiglobulin test or IAT) is used to detect very low concentrations of antibodies present in a patient's plasma/serum prior to a blood transfusion.
The IAT is a two-stage test.
Stage 1 : Test RBCs washed and incubated with a test serum. If the serum contains antibodies to antigens on the RBC surface, the antibodies will bind onto the surface of the RBCs.
Stage 2: RBCs are then washed well with saline and then incubated with antihuman globulin. If antibodies have bound to RBC surface antigens in the first stage, RBCs will agglutinate when incubated with the antihuman globulin and the indirect Coombs test will be positive. By diluting the serum different titrations can be measured.
Most common uses of the IAT are : 1) To screen pregnant women for antibodies that may cause hemolytic disease of the newborn. 2) To test donor blood for compatibility.
The IAT is a two-stage test.
Stage 1 : Test RBCs washed and incubated with a test serum. If the serum contains antibodies to antigens on the RBC surface, the antibodies will bind onto the surface of the RBCs.
Stage 2: RBCs are then washed well with saline and then incubated with antihuman globulin. If antibodies have bound to RBC surface antigens in the first stage, RBCs will agglutinate when incubated with the antihuman globulin and the indirect Coombs test will be positive. By diluting the serum different titrations can be measured.
Most common uses of the IAT are : 1) To screen pregnant women for antibodies that may cause hemolytic disease of the newborn. 2) To test donor blood for compatibility.
Direct Coombs Test Or Direct Antiglobulin Test
The direct Coombs test (also known as the direct antiglobulin test) is used to detect antibodies on the RBC surface. A positive Coombs test indicates that an immune mechanism is attacking the patient's own RBC's. This mechanism could be autoimmunity, alloimmunity or a drug-induced immune-mediated mechanism.
The patient's RBCs are washed and then incubated with antihuman globulin. If immunoglobulin or complement factors have been fixed on to the RBC surface in-vivo, the antihuman globulin will agglutinate the RBCs and the direct Coombs test will be positive.
Examples of diseases that give a positive DAT: Rh isoiimunization, ABO disease, autoimmune hemolytic anemis (warm and cold type) and drug induced hemolysis.
The patient's RBCs are washed and then incubated with antihuman globulin. If immunoglobulin or complement factors have been fixed on to the RBC surface in-vivo, the antihuman globulin will agglutinate the RBCs and the direct Coombs test will be positive.
Examples of diseases that give a positive DAT: Rh isoiimunization, ABO disease, autoimmune hemolytic anemis (warm and cold type) and drug induced hemolysis.
Causes of Acquired Polycythemia
- Generalized or localized tissue hypoxia
- Generalized
- high altitudes
- COPD
- Alveolar hypoventilation/Obstructive Sleep apnea or Obesity (Pickwickian syndrome).
- Right-to-left shunt/Congenital heart disease
- High affinity hemoglobinopathy. Carbon monoxide poisoning (causes formation of carboxyhemoglobin which has a strong affinity for oxygen.)
- Decreased perfusion of the kidneys, which may lead to stimulation of erythropoietin
- Arteriosclerosis
- Renal transplantation
- Aneurysms of the aorta and renal vessels
- Generalized
- Inappropriate stimulation of EPO production
- Hydronephrosis and cysts, can stimulate erythropoietin production
- Malignant and benign tumors that secrete erythropoietin e.g. renal carcinomas and cerebellar hemangioblastomas
- Blood doping(competitive sportsman)
- Androgenic steroid use.
- Congenital causes of high erythropoietin e.g. in von Hippel-Lindau syundrome
- Low EPO-dependent polycythemias
- These are called primary familial and congenital polycythemias.9
- The EPO receptor mutation results in a gain of function, and patients have normal-to-high hematocrit values and low EPO levels.10
- These conditions can be acquired from (1) insulinlike growth factor-1 (IGF-1), a well-known stimulator of erythropoiesis, and (2) cobalt toxicity, which can induce erythropoiesis.
Post Mastectomy Lymphedema
Post Mastectomy Lymphedema predisposes to development of lymphangiosarcoma many years after the surgery.
RhoGAM for ITP
Rh +ve patients can be treated with RhoGAM. This treatment (with products such as WinRho, Rhophylac or RhoGAM) is normally used for Rh-negative women during pregnancy and after the birth of an Rh-positive infant to prevent sensitization to the Rh factor, but has been found to be effective on some Rh-positive ITP patients. Treatment with anti-D is costly, produces a short-term improvement and is not recommended for post-splenectomy patients. It acts by blocking Fc receptors on the macrophages thereby preventing phagocytosis of antibody coated platelets.
Mesothelioma
Malignant mesothelioma has a strong association with asbestos exposure. It has a peak incidence 35-45 years after asbestos exposure. Although mesothelioma occurs much more frequently in men exposed to asbestos the most common tumor in this population is Squamous cell carcinoma. Mesothelioma has many occupational health and legal implications. It is one of the common reasons for employer-employee law suits.
Acute Lymphoblastic Leukemia
Following puts a child with ALL in high risk category and hence has worse prognosis.
1) Age <1 or >10 at diagnosis
2) WBC at diagnosis >50,000
Rasburicase
Rasburicase is used in the management of Tumor Lysis Syndrome. It is an enzyme called urate-oxidase. It is naturally present in many animals but not in humans. Rasburicase catalyses the conversion of uric acid to allantoin. Allantoin is an inactive metabolite of purine metabolism, and is 5 to 10 times more soluble than uric acid, so renal excretion is more effective.
Contraindications: Pregnancy, G6PD deficiency.
Typical adverse effects of Chemotherapeutic agents
Vincristine : Neuropathy
Dauno/doxorubicin : Cardiomyopathy
L-asparaginase : Acute Pancreatitis
Cyclophosphamide : Hemorrhagic cystitis
Busulphan : Lung damage
Methotrexate : Mucositis
Each of these side effects is quite typical. One can expect an occasional question in the USMLE but these are not heavily tested.
Dauno/doxorubicin : Cardiomyopathy
L-asparaginase : Acute Pancreatitis
Cyclophosphamide : Hemorrhagic cystitis
Busulphan : Lung damage
Methotrexate : Mucositis
Each of these side effects is quite typical. One can expect an occasional question in the USMLE but these are not heavily tested.
Thrombotic thrombocytopenic purpura
TTP can TEAR you apart.
Thrombocytopenia
Encephalopathy
Anemia (microangiopathic, hemolytic)
Renal failure
Thrombocytopenia
Encephalopathy
Anemia (microangiopathic, hemolytic)
Renal failure
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