Hematology 2 Flashcards
Normal Hb in Children
11 + 0.1(Age in years)
Lower Normal MCV in Children
70+ Age in years up to 80.
Ferritin below __ is highly specific for IDA
15
B Thalassemia
One locus on each chromosome 11. Microcytosis out of proportion to the degree of anemia.
A Thalassemia
Two loci on each chromosome 16.
One defective alpha thal gene
Asymptomatic carrier
Two defective alpha thal genes
Alpha thalassemia minor, target cells. Normal Hb electro
Three defective alpha thal genese
Hb H (Clumped chains), leads to hemolytic anemia. Tx: Splenectomy and transfusions
Four defective alpha thal genes
No functional Hb, not compatible with life.
Transient Erythroblastopenia of Childhood (TEC)
Pure red cell aplasia. Occurs in healthy young children 6mo to 6 years. Normocytic anemia with low Hb but normal non RBC cell lines. Spontaneous recovery.
Diamond Black Fan Anemia
Pure red cell aplasia. Severely low Hb, macrocytosis, low rets, otherwise normal cell lines. 30-50% congenital abnormalities.
HbSS
SCD Only HbS, severe symptoms
HbSBo
SCD No HbA, severe symptoms
HbSB+
SCD Some HbA, milder symptoms
HbSC
SCD HbS and HbC present, milder symptoms.
Severe SCD manifestations
Splenic infarction, functional asplenia, low Hb, vasooclussion.
Aplastic crisis
cessation of erythropoeisis often due to parvovirus B19. Increased anemia, decreased reticulocytes.
SCD Painful episodes
triggered by cold, dehydrations, stress, alcohol, but usually no obvious cause.
Acute Chest Syndrome
SCD most common cause of death. Peak incidence between 2 and 4 years old. Dx: New infiltrate with chest pain or fever or resp distress.
Hereditary Spherocytosis
Hemolytic anemia, spenomegaly, jaundice, normal MCV, ELEVATED MCHC, elevated retics.
Compared with _______ transfusion strategies, _________ strategies resulted in better patient outcomes.
Liberal (10hb), Restrictive (7hb)
Indications for Plasma transfusion
Correction of major bleeding, Deficiency in multiple coagulation factors, Massive transfusion protocol
Cryoprecipitate contains:
Factor VIII, Factor XIII, Fibrinogen, vwF
Cryoprecipitate is used for:
Fibrinogen replacement in bleeding, when normal treatment medications are not available for vWF disease, or factor 8/13 deficiency.
Recombinant Factor VIII
Used in Hemophilia to prevent bleeding episodes and preoperative management.
Prothrombin Complex Concentrate
Contains vitamin K dependent factors: 2, 7, 9, 10
Used in hemophilia patients experiencing hemorrhage or to control perioperative bleeding.
IVIG
SCIDS, agammaglobulinemia
Albumin
Hypoalbunemia, sometimes volume replacement.
Febrile TR
Temp increased by 1C from the pretransfusion value during or up to 4 hours post transfusion. More frequent in plasma.
Allergic TR
Allergens from the donor, more likely in plasma. Urticaria and Pruritus within 4 hours. Treat with Diphenhydramine. This is the only time of TR where treatment can be restarted.
Anaphylaxis TR
Antibodies to something in the component, usually IgA. Fast HR and low BP. Stop tranfusion and place in trendelenburg. Use washed products.
TACO
Can occur within 6 hours, but usually happens during the transfusion. Causes pulmonary edema, increased BP and HR, hypoxia. Patient will have elevated BNP and bilateral “White Out” infiltrates. Treat by stopping transfusion, reverse trendelenburg, O2, and diuretics.
TRALI
Reaction requiring neutrophils to be primed and present in large numbers in the lungs. The neutrophils then react to the tranfusion and cause damage to lung tissue. Difficulty breathing, fever, chills.
TRALI Diagnosis Criteria
- No evidence of previous acute lung injury
- Acute lung injury within 6 hours of tranfusion
- Hypoxemia
- Bilateral infiltrates
- No evidence of TACO
- No risk factors for ALI/ARDS
Acute Hemolytic TR
RBC lysis by antibodies. Usually an ABO discrepancy. Almost always a clerical error. Triad: Fever, flank pain, red or brown urine. Tx: stop transfusion, IV saline, support.
Delayed Hemolytic TR
Development of new antibodies to RBCs. Occurs 3 to 30 days post transfusion. Should inform the patient for future transfusions.
Posttransfusional Purpura
Extremely rare, antiplatelet antibodies destroys tranfused platelets as well as host platelets. Tx: IVIg
Endothelin
Following injury, this triggers localized vasoconstriction.
_______ on the platelet binds to ________ on the subendothelium allowing for initial platelet adhesion and activation.
GpIb, vWF
vWF will bind to ________ in addition to GpIb.
Factor VIII, allows for accumulation at site of injury
______ On the platelet membrane binds to collagen
integrin alpha2beta1
Platelet activation causes these changes
Spiny shape, negatively charged phospholipids migrate to the platelet surface, release of dense and alpha granules, production and release of thromboxane A2.
Contents of alpha granules
Coagulation proteins (vWF, and Factor V) Wound healing proteins (fibronectin, PDGF)
Contents of dense granules
ADP, ATP, Ca2+, 5HT, Epi
______ Triggers change in conformation of GpIIb-GpIIIa receptor in platelet membrane which allows fibrinogen.
ADP
von Willebrand Disease
lowered vWF levels and function, reduced factor VIII. Managed with desmopressin. Type 1: most common, reduced vWF amount. Type 2: qualitative deficiency if vWF. Type 3: complete deficiency of vWF.
Desmopressin
induces release of vWF and factor VIII
Bernard-Soulier syndrome
Failure of platelets to aggregate in response to stimuli. Defective interaction between vWF and GpIb. Giant platelets in PBS.
Glanzmann thrombasthenia
Quantitative or qualitative defect in GpIIb/GpIIIa. Platelets won’t aggregate.
These clotting factors contain y-carboxyglutamate (Calcium chelator)
Prothrombin, VII, IX, X
The enzyme that converts glutamate to y-carboxyglutamate requires ________ as a cofactor.
Vitamin K
Warfarin
Blocks Vitamin K epoxide reductase, preventing the recycling of Vitamin K and production of y-carboyxglutamate.
Tissue Factor (Factor III)
Part of the initiation complex for the clotting cascade. Membrane bound, in the presence of Ca2+ will bind and activate factor VII.
Factor VII
Part of the initiation complex foe the clotting cascade. Activated by tissue factor in the presence of calcium. Once activated, will cleave factor X into factor Xa.
Factor X
Part of the initiation complex for the clotting cascade. Activated by VIIa. Once active, it slowly cleaves prothrombin to thrombin. Complexes with Va and Ca2+ to rapidly cleave prothrombin to thrombin.
Thrombin
Activated from prothrombin by factor Xa. Activates factors V, VIII, and IX. Converts Fibrinogen to fibrin. Converts factor XIII to XIIIa.
Factor V
Activated by thrombin. Complexes with Xa and calcium to rapidly cleave prothrombin to thrombin.
Factor VIII
Activated by thrombin. Forms a complex with IXa and calcium which quickly activates factor X.
Factor IX
Activated by thrombin and XIa. Forms a complex with VIIIa and calcium which quickly activates factor X.
aPPT
Intrinsic pathway. assess function of factors IX, XI, VIII, X, V, prothrombin, fibrinogen.
Factor XI
Activated by thrombin, cleaves IX to IXa.
PT
Extrinsic pathway. Assesses function of VII, X, V, prothrombin, and fibrinogen.
Hemophilia A
Factor VIII deficiency
Hemophilia B
Factor IX deficiency
Factor XIII
Activated by thrombin. cross links the fibrin clot to form a hard clot.
Thrombomodulin
Alters the activity of Thrombin to activate protein C.
Protein C
activates and binds protein S. Stimulates t-PA release.
Protein C/S Complex
degrates factor Va, and VIIIa
Factor V Leiden
Factor V that is resistant to cleavage by protein C/S. R506G mutation. Increased risk of hypercoagulation. 50% of inherited thrombophilia.
Antithrombin III
Serpin. Binds Heparin and inhbits thrombin. Heparin-ATIII complex inhibits IXa, Xa, XIa, and XIIIa.
Tissue Factor Pathway Inhibitor
Produced by endothelial cells, inhibits factor VIIa and Xa.
Tissue Plasminogen Activator
Activates plasminogen to plasmin, secreted by endothelial cells, binds to fibrin clots. Inhibited by alpha 2 antiplasmin and alpha2 macroglobulin.
Clopidogrel (Plavix)
Prevents ADP binding the platelets
GpIIb-GpIIIa Inhibitors
Abciximab (Reopro), Eptifibatide (Integrellin), Tirofiban (Aggrastat)
ITP
Immune Thrombocytopenic Purpura. Platelet destruction by autoantibodies. Associated with a viral prodrome. Low platelets in the absence of other defined causes. Tx: IgG, Steroids
TTP
Thrombotic Thrombocytopenic Purpura. Huge monomers of vWF that attract platelets due to ADAMTS-13 deficiency. Causes narrowing of vessels that shear RBCs into “Helmet Cells”. Consumption coagulopathy. 90% fatal if untreated.
TTP Triad
Thrombocytopenia, Microangiopathic Hemolytic Anemia, Neurological Findings, Renal Insuficiency, Fever.
Hemolytic Uremic Syndrome
Most common cause of acute renal failure in children. Secondary to Shiga toxin. Toxin adheres to neutrophils and platelets, carried to golmerulus, stimulates formation of huge vWF monomers which cause microangiopathic hemolytic anemia. Tx: treat infection, tranfusion, fluids.
Heparin Induced Thrombocytopenia
Autoantibodies against heparin antigen complex. Type I is transient, type II is bad. Can cause thrombosis.
Heparin
Increases antithrombin activity by 1000 fold. Antithrombin inactivates thrombin and Xa.
Hemophilia C
Factor XI deficiency, autosomal recessive
Virchow Triad
Factors predisposing thrombosis. Endothelial injury, blood stasis or turbulence, blood hypercoagulability.
___________ and __ are produced by the endothelium and prevent platelet adhesion.
PGI2 and NO
Cardiac and Arterial Thrombi
Possible emoblism to brain, kidneys, spleen.
When to further investigate thrombosis
Young patients, family history of thrombosis, thrombosis in absence of known risk, recurrent miscarriages, warfarin-induced skin necrosis, neonatal purpura fulminans.
Common inherited thromophilias
Antithrombin deficiency, Protein C and S deficiencies, Factor V leiden, and prothrombin G20210A mutation.
Antithrombin Deficiency
Autosomeal dominant, Q/Q defects, thrombotic phenomena at an early age, PE is often first manifestation.
Protein C deficiency
Autosomal dominant/recessive. QQ defects. Homozygotes die in infancy, skin necrosis with warfarin.
Protein S deficiency
Autosomal dominant, QQ defects, homozygotes die in utero or in early infancy from NPF. Skin necrosis with warfarin.
Neonatal Purpura Fulminans
Manifestation of homozygous protein C/S deficiencies. Lethal syndrome of DIC. Skin lesions progress to full thickness necrosis that is irreversible.
Prothrombin G2021A mutation
Noncoding mutation, results in 5-10% high levels of prothrombin. 2-3x risk of venous thromboembolism. 5-7% of young patients with DVT/PE.
Acute Leukemias
ALL and AML. Both present with pancytopenia. Tumor cells displace healthy cells in bone marrow.
Acute Myeloblastic Leukemia
Most common leukemia in adults.
ALL
B-ALL and T-ALL. B-ALL is 85% of cases. Most common in children, tumors are aggressive.
Polycythemia Vera
Jak2 mutation. High levels of functional RBCs. 1 year survival without treatment. Tx; Blood removal and chemotherapy.
Essential Thrombocythemia
Jak2 or MPL mutations. Too many megakaryocytes. Usually asymptomatic until after 50 years old.
Primary Myelofibrosis
Jak2 or MPL mutations. Fibrosis and atypical megakaryocytes. Median survival from 1 to 8 years.
Chronic Myelogenous Leukemia
CML. Fusion of BCR-ABL gene. Overgrowth of granulocytic and megakaryocytic precursors in bone marrow. No treatment will result in acute leukemia within 5 years. Tx: drugs that target BCR-ABL gene (Imatinib) or stem cell transplant.
Myelodysplastic syndrome
Cancer in which bone marrow does not make enough healthy blood cells and there are abnormal cells in blood or bone marrow. Can convert to AML.
Hodgkin Lymphoma
Reed-Sternberg cells present. Usually arises from a single lymph node and spreads in a predictable way. Radiation and chem have a 60 to 90% cure rate.
Non Hodgkin Lymphoma
Over 50 types. Range from slow growing to very aggressive.
Chronic Lymphocytic Leukemia
Not associated with chromosomal translocaiton. Median age of diagnosis is 70. Increased number of small round lymphocytes. Smudge cells. Common to be asymptomatic at diagnosis. 5-11 year median survival.
Multiple Myeloma
Median onset 50-60 years. Mature B cells. Rouleaux formation on the blood smear. Tumors produce partial antibodies which can be detected. Lytic Bone lesions.
Solitary Plasmacytoma
Solitary mass consisting of a clonal plasma cell tumor. Does not usually produces antibodies. Can progress to multiple myeloma.
Primary Amyloidosis
Clonal expansion of plasma cells in the bone marrow that secrete monoclonal light chains. These chains misfold and from deposits in tissue.
Monocolonal gammopathy of uncertain significance
Detection of monocolonal immunoglobulin protein in the serum without evidence for malignancy of B cells. Risk of progression to multiple myeloma.
Auer Rods
Morphology of Acute Myelogenous Leukemia
Induction Therapy
Initial chemo dose, goal is to induce remission by killing cells to an undetectable level.
Consolidation Therapy
Follow up dose to kill off undetectable cancer cells.
Maintenance Therapy
Therapy given after patient as achieved remission. Prevents relapse.
Oncologic Emergency
Pathologic spinal cord compression, superior vena cava syndrome, gynecologic bleeding
Normal tissues at risk from acute radiation side effects
Bone marrow, GI mucousa, skin
3 types of external beam radiation
Photons (Xrays), Electrons, and Heavy charged particles (protons and carbon)
Linear Accelerator (LINAC)
Accelerates electrons to collide with heavy metals to produce Xrays.
Applications of proton therapy
Pediatric tumors, CNS tumors, Skull base and paraspinal tumors, lung, head and neck, prostate.
Radiosensitive tumors
lymphoma, seminoma
Radioresistant tumors
head, neck, prostate, glioblastoma
