Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
174 Cards in this Set
- Front
- Back
Steps of Primary Hemostasis
(5) |
1) Enodthelin induced vasospasm
2) vWF binds exposed collagen 3) Plts bind vWF via Gp1b 4) Plts release ADP -->exposes GPIIb/IIIa; and TXA2 5) Fibrinogen links plts together via GPIIb/IIIa |
|
Where does vWF come from?
|
Weibel-Pallade body of enodthelial cells and plts
|
|
What do plt mediators do?
1) ADP 2) GPIIb/IIIa 3) TXA2 |
1) ADP promotes exposure of GPIIb/IIIa
2) GPIIb/IIIa links plts via fibrinogen 3) TXA2 promotes plt aggregation |
|
Petechiae indicates what re plts?
|
Decreased plt NUMBER, not quality.
|
|
Etiology
ITP Idiopathic Thrombocytopenic Purpura |
IgG Autoimmune destruction of plts
|
|
Dx
Thrombocytopenia in CHILD, after viral INFXN, self limited |
Acute ITP
|
|
Dx
Women of childbearing age, low plts, transient low plts in newborn |
Chronic ITP
|
|
Tx
ITP (3) |
1st) Corticosteroids
2nd) IVIG (temporary) Refractory) Splenectomy (spleen is where plts destroyed in ITP) |
|
Etiology
Microangiopathic Hemolytic Anemia |
-Pathologic formation of MICROTHROMBI shear RBCs as they flow past in small vessels --> hemolytic anemia
|
|
Dx
Schistocyte |
MAHA
Microangiopathic hemolytic anemia |
|
Causes of Microhemolytic anemia
|
1) TTP (Thrombocytopenic Purpura)
2) HUS (Hemolytic Uremic Sx) |
|
Etiology
TTP Thrombocytopenic purpura |
DECREASED ADAMS 13 leading to inability to breakdown vWF multimers --> build up --> abnormal plt adhension --> inappopriate microthrombi --> MAHA
|
|
Etiology
HUS Hemolytic uremic sx |
E.coli O157 infxn --> verotoxin --> damages endothelial cells --> plt microthrombi --> MAHA
|
|
HUS exposure
|
CHILDREN to undercooked beef with E. coli O157
|
|
Dx
Skin and mucosal bleeding, hemolytic anemia, fever, renal insufficiency, CNS abnormalities |
MAHA from either TTP or HUS
TTP = primarily CNS HUS = primarily renal (uremia) |
|
Dx
Low plts, hi BT, NORMAL PT/PTT, anemia with schistocytes |
MAHA from TTP or HUS
(normal PT/PTT bc coag cascade never activated so not depleted) |
|
Etiology
Bernard-Soulier Sx |
GPIb deficiency --> can't bind vWF --> no plt adhesion to injury
|
|
Dx
Enlarged plts on smear |
Bernard Soulier sx
|
|
Etiology
Glanzmann Thrombasthenia |
GIIb/IIIa def. --> plts cannot stick together
|
|
MOA
ASA anti-plt |
ASA inhibits COX --> no TXA2 --> NO plt aggregation
|
|
Steps of Secondary Hemostasis
|
1) Coag cascade makes THROMBIN
2) Thrombin converts fibrinogen to FIBRIN 3) Fibrin cross links with itself to stabilized plug |
|
Dx
1) Skin and mucosal surface bleeding 2) Deep tissue (muscle and joint) bleeding |
1) Primary hemostasis disorder (plt problem)
2) Secondary hemostasis disorder (coag problem like hemophilia) |
|
Coag cascade memorize now
|
12, 11, 9, 8 |X| 7
5,2,1 SEC, PTT, HEP v |
|
Etiology
Hemophilia A |
FVIII (Aeight) deficiency
|
|
Dx
1) Hi PTT, nl PT, lo FVIII, nl plts, nl BT 2) if Hi VIII, lo IX 3) If doesn't fix with blood mixing |
1) Hemophilia A
2) Hemophila B 3) Coagulation factor inhibitor |
|
Etiology
Hemophilia B |
FIX deficiency (Be Mine/nine)
|
|
Dx
Hi BT, hi PTT, nl PT, abnormal ristocetin test |
vWF deficiency
(vWF stabilized FVIII so increases PTT) |
|
Tx, MOA
vWF disease |
Desmopressin
MOA) Desmopressin increases vWF release from Weibel-Pallade bodies of endothelial cells |
|
MOA
Warfarin |
Blocks Vitamin K Epoxide Reductase preventing reuse of vit K
|
|
Liver failure increases what coag number
|
PT
|
|
Etiology
HIT Heparin induced Thrombocytopenia |
Heparin induces plt destruction --> sometimes activates other plts -->thrombosis
|
|
Etiology DIC
(2) |
1) Inappropriate activation of coag cascade --> microthrombi everywhere --> ischemia/infarction
2) Also consumes plts and coag factors --> bleeding |
|
Causes of DIC
|
1) Obstetric complication
2) Sepsis 3) Adenocarcinoma 4) Acute promyelocytic leukemia 5) Rattlesnake bite |
|
Dx
Lo Plts, Hi PT/PTT, lo fibrinogen, elevated D-dimer, MAHA |
DIC
|
|
Dx
Hi PT/PTT, hi BT, nl Plts, Increased fibrinogen split products without D-dimers |
Plasmin Overactivity
(no D-dimer bc no thrombus was ever made, just overactive plasin cleaving fibriogen not fibrin) |
|
MOA
tPA (so really plasmin) (3) |
Activates Plasmin which does:
1) Cleaves FIBRIN and FIBRINOGEN 3) Destroys Coag Factors 4) Blocks plt aggregation |
|
Causes of
Plasmin overactivity |
1) Radical prostatectomy (release of urokinase activates plasmin)
2) Liver cirrhosis (decreased anti-plasmin production) |
|
Dx
No Lines of Zahn |
Postmortem clot
|
|
Causes of High homocysteine
(3) |
1) Vit B12 def
2) Folate def 3) CBS def (cystathionine beta synthase) |
|
Dx
Vessel thrombosis, mental retardation, lens disolcation, long slender fingers |
Homocystinuria due to CBS def
|
|
Etiology
Protein C or S def |
Protein C and S normally inactivate FV and FVIII, KO --> hypercoagulable state
|
|
Vitamin K dependent factors
|
10,9,7,2, C and S
|
|
Etiology
Warfarin skin necrosis Tx? |
Initial warfarin knocks out new production 10,9,7,2 and C/S but C/S decrease first so hypercoagulable.
Bridge with HEPARIN for 3 days |
|
Etiology
Factor V Leiden |
Mutated FV cannot be deactivated by Proteins C or S --> hypercoagulable
|
|
Etiology
ATIII deficiency |
Heparin like molecules activate ATIII normally, but if ATIII KO can't inactivate thrombin --> hypercoagulable
|
|
MOA
Heparin |
Activates ATIII which inactivates thrombin
|
|
Initial anti-coag for ATIII def patients
|
Give HIGH DOSE HEPARIN (bc not much ATIII to activate) to bridge to nL warfarin dose.
|
|
What happens to PTT with heparin if pt ATIII def?
|
Nothing
|
|
Dx
Dyspnea, petechiae over chest |
Fat embolism
|
|
Dx
SOB, neurologic sx, DIC, keratin debris in embolus, |
Amniotic emboli
|
|
Dx
SOB, hemoptysis, pleuritic CP, pleural effusion, D-dimer |
Pulmonary embolus
|
|
Complication of chronic pulmonary emboli
|
Pulmonary HTN
|
|
Normocytic range
|
80-100
|
|
What causes microcytosis?
|
An extra division after erythroblast stage 2/2 decreased total Hb (attempt to maintain correct Hb concentration inside cell)
|
|
Hemoglobin has what components that lead to microcytosis?
|
Heme = Fe + protoporphyrin
Globin |
|
All causes of Microcytic anemia
|
1) Iron def
2) Anemia of chronic disease (sequester iron problem) 3) Sideroblastic (porphoryin problem) 4) Thalassemias (globin problem) |
|
Where is Fe absorbed?
|
Duodenum absorbs and puts into blood via Ferroportin
|
|
What does Transferrin do?
|
Transports Fe to liver and bone marrow macros for storage
|
|
What does Ferritin do?
|
Stores intracellular Fe (to avoid free radicals)
|
|
What do Fe studies tell us?
Serum Fe TIBC % Saturation Serum Ferritin |
Serum Fe - Total Fe on transferrin in blood
TIBC - Total Transferrin in blood % Saturation - Percent of Transferrin with Fe (about 1/3) Serum Ferritin - Total Fe in cells |
|
Stages of Iron Def
|
1) Stored Fe is depleted (Ferritin goes down, TIBC goes up)
2) Serum Fe is depleted (Serum Fe goes down, % sat goes down, 3) Normocytic anemia 4) Micocytic, hypochromic anemia |
|
Relationship between Ferritin and TIBC
|
Inversely proportional
|
|
Dx
High Free Erythyrocyte Protoporphyrin |
Iron def anemia
(Normal porphyrin production outpaces lack of Iron in heme production) |
|
What size are RBCs
|
The size of lymphocyte nucleus
|
|
Mechanism Chronic disease anemia
(2) |
Chronic disease --> Hepcidin binding of Ferroportin on Enterocytes and Marcophages --| Fe transport
1) Sequesters Fe preventing macrophagic transport to erythroid precursors 2) Also suppresses FEP |
|
Fe studies in Anemia of Chronic Disease
ferritin, TIBC, Serum iron, Saturation FEP (Free erythrocyts protoporphyrin) |
Hi ferritin, lo TIBC,
Lo serum iron, lo saturation Hi FEP |
|
Where is heme made in the cell?
|
Mitochondria
Ring Sideroblast: Hence sideroblastic anemia is ring of Iron in Mito around nucleus |
|
Congenital sideroblastic anemia defect
|
delta-ALA Synthase (1st step in protoporphyrin synth)
|
|
Acquired causes of Sideroblastic anemia
|
1) EtOH
2) Pb 3) Vit B 6 def (needed for ALAS in protoporphyrin synth) |
|
Fe studies in Sideroblastic Anemia
ferritin, TIBC, Serum iron, Saturation |
Iron overloaded state:
Hi ferritin, Lo TIBC Hi Serum Fe, Hi %sat |
|
Etio of Alpha Thalassemia
|
Gene DELETION of alpha globin copy(ies) (1-4)
|
|
Alpha thalassemia 2 losses:
Cis: Trans: |
Cis: Asians (worse for offspring)
Trans: Africans |
|
What is HbA
What is HbA2 What is HbH What is HbF What is Hb Barts? |
HbA: normal, A2B2
HbA2: normal, A2D2 HbH: In alpha thal, B4 Hb Barts: Complete alpha thal (fatal), Gamma4 |
|
Etiology of Beta thalassemia
|
Gene MUTATIONS of 1-2 beta copies
Beta 0 = KO Beta + = Decreased production |
|
Dx
Target cell |
Beta thalassemia
Minor or major OR Sickle cell anemia |
|
Dx
Expansion of hematopoesis into marrow and facial bones (if skull = crew cut appearance), liver, spleen |
Beta thal major
|
|
Tx
Beta thal major |
Chronic transfusions
|
|
Mech of Macrocytic anemia
|
1 Less division occurs of erythroblast lineage 2/2 to lack of DNA precursors bc of lack of THF (Folate) or VitB12
|
|
How many lobes in a Neutro is normal
|
Up to 5
(Hypersegmented is like 7) |
|
Causes of Macrocyctic Anemia
Hyperseg Neutros (2) Normal Neutros (3) |
Hyper: Folate or VitB12 def
Normal: 1) EtOH 2) Liver Disease 3) Drugs (5-FU) |
|
Where is Folate absorbed
|
Jejunum
|
|
Dx
Glossitis, Inc serum Homocysteine, nL Methylmalonic acid Dx " " except Hi Methylmalonic acid causing degeneration of spinal cord |
1) Folate def
2) VitB12 def |
|
How is B12 absorbed
|
Binds to R binder, cleaved in small bowel, binds to IF and travels to Ileum where absorbed
|
|
Etio Pernicious Anemia?
|
Autoimmune destruction of Parietal cells of stomach so can't make IF for VitB12 absorption
|
|
Causes of B12 def?
|
1) Pancreatic insufficiency (can't release from R binder)
2) Damage to terminal ileum (e.g. Crohn's) 3) Long term veganism 4) Pernicious anemia |
|
Why are reticulocytes bluish?
|
The RNA stains blue
|
|
Retic correction Eq
And cutoff |
Retic count x Hct/45 = corrected retic count
If anemic, normal is over 3% |
|
How are RBCs degraded?
(3) |
Macros digest engulfed RBCs
1) Globin --> a. acids 2) Heme --> Fe (recycled) and 3) Protoporphyrin --> Unconj bilirubin |
|
Dx
Decreased haptoglobin, hemosiderinuria |
Intravascular hemolysis
When haptoglobin is overwhelmed Hb deposits into cells of renal tubules, sloughing off later as hemosiderin |
|
Etio of
Hereditary Spherocytosis |
Deficiency of Spectrin, Ankyrin, or Band 3.1
(proteins that tether cytoskeleton to membrane for disc shape) |
|
Dx
Inc RDW, and Inc MCHC |
Hereditary spherocytosis
Blebs are removed form membrane leading to different sizes. Reduction of membrane without losing contents concentrates the Hgb. |
|
Increased risk for all hemolytic anemias
|
Bilirubin gallstones
|
|
Increased risk for all anemias with limited RBC reserves
|
Parvovirus induced Aplastic Anemia
|
|
How to diagnose
Hereditary Spherocytosis |
Osmotic fragility test
|
|
Tx
Hereditary Spherocytosis |
Splenectomy
|
|
Sickle cell is on what gene
|
Beta globin gene
|
|
Mechanism of
Sickle cell pathology (1+2) |
HbS polymerize when deoxygenated -->
1) Needles prick the membrane 2) Irreversible sickling vasoocclusive crises --> swollen hands and feet, and Autosplenectomy |
|
MOA
Hydroxyurea in sickle cell |
Increases HbF by uknown mechanism
HbF doesn't sickle (no Beta globin involved) |
|
Sickle cell has increased risk of what infxn?
|
Salmonella paratyphi osteomyelitis
|
|
Etio of
Acute Chest Sx in sickle cell |
Vaso-occlusion in pulmonary microcirculation --> increased transit time --> ischemic feeling
|
|
Renal manifestation of sickle cell
|
Renal papillary necrosis (vaso-occlusive) --> hematuria and proteinuria
|
|
Why don't sickle cell trait have sx?
|
Hbs is made less than HbA (only about 45%) and 50% needed to sickle --> asymptomatic
EXCEPT in renal medulla |
|
Only complication of sickle cell trait
|
Renal medulla's EXTREME hypoxia and hypertonicity cause even sickle trait to sickle --> microinfarctions --> microscopic hematuria --> eventual inability to concentrate urine
|
|
Dx
Metasulbite screen |
Both Sickle disease and Trait will sickle
|
|
Mech
Hemoglobin C |
Glu --> Lysine point replacement in Beta globin --> HbC crystals on blood smear
|
|
What protects RBC from Complement?
(2) |
DAF and MIRL
|
|
Mech
Paroxysmal nocturanal hematuria (2) |
1) Deficiency of GPI which attaches DAF and MIRL to RBC
2) At night shallow breathing --> slight acidosis --> activates complement a little --> no GPI so no DAF --> complement destroys RBCs, WBCs, and plts |
|
Dx study
Paroxysmal Nocturnal Hematuria |
CD55 lacked in PNH
|
|
Cause of death in
Paroxysmal Nocturnal Hematuria |
Plt destruction --> thrombosis of Hepatic or Cerebral veins
|
|
High risk in PNH
|
AML develops in 10% due to pre-existing mutation in myeloid precursor
|
|
Mech
G6PD def |
G6PD cannot reduce Glutathione back --> Hgb gets oxidized --> splenic macros turn them into BITE CELLS --> Intravascular Hemolysis
|
|
Variants of G6PD
|
African: Mild, G6PD 1/2 life mildly shorter, only old RBCs have damage
Mediterranean: Severe, G6PD 1/2 markedly shorter, wide RBC damage |
|
Dx
Hemoglobinuria, back pain |
G6PD def
Hgb is nephrotoxic --> back pain |
|
Mech
Warm (IgG mediated) Autoimmune Hemolytic Anemia |
IgG binds RBCs --> splenic macros eat membrane ---> spherocytes --> Extravascular Hemolysis in spleen
|
|
Mech
IgM |
IgM fixes complement on RBCs in cold extremities
|
|
Associated with IgM Autoimmune Hemolytic Anemia (AIHA)
|
1) Mycoplasma pneumoniae
2) EBV |
|
How does Direct Coomb's test work
What does it answer? |
If RBC is ALREADY coated with Ig, the ADDED IgG will bind --> Agglutination
Answers: Do RBCs already have Ig on them? Tests for Autoimmune Hemolytic Anemia (AIHA) |
|
How does Indirect Coomb's test work
What does it answer? |
Add IgG and fresh RBCs to Pt's serum. If Abs to RBCs present, IgG will bind --> Agglutination
Answers: Are Abs to RBC in BLOOD? |
|
What mosquito spreads Malaria?
|
Anopheles
|
|
What is a myelophthisic process?
|
A pathologic process that replaces bone marrow --> Pancytopenia
|
|
Cortisol causes lymphocyte destruction
|
!
|
|
Causes of neutrophilic leukocytosis
(3) |
1) Bacterial infxn
2) Tissue necrosis 3) Hi Cortisol (disrupts neutro storage marginilaztion) |
|
What CD marker marks Left shift in Neutros
|
Lo CD16 (i.e. lack of Fc receptor on immature neutros)
|
|
Causes of Eosinophilia
(3) |
1) Allergic rxn
2) Parasitic infxn 3) Hodgkin lymphoma |
|
Associated with Basophilia
|
CML
|
|
Causes of Lymphoctyic Leukocytosis
|
1) Viral infxns (not bacterial!!)
2) Bordetella pertussis (1 bacterial exception) |
|
How monospot works
|
If EBV infxn --> Herterophile Abs will cause xenogenous RBCs to agglutinate
Will NOT be positive if CMV is causing infectious mononucleosis |
|
Complications of Infectious mononucleosis
(3) |
1) Splenic rupture
2) PCN induced rash 3) Dormany in B cells --> Lymphoma |
|
Markers for Acute Leukemia
tDt Myeloperoxidase |
tDt = ALL (Acute leukemia of Lymphoblasts)
Myeloperoxidase = AML (Acute leukemia of Myeloblasts) *MPO becomes Auer Rods |
|
Dx
CD10, Cd19, and CD20 CD2-8, no CD10 |
B-ALL
T-ALL |
|
Tx
B-ALL |
Chemotherapy + to Scrotum and CSF
(Can't cross those specialized blood barriers) |
|
B-ALL translocations and prognoses
Children Adults |
Children - t(12,21) good
Adults - t(9,22) (Ph+ ALL) bad |
|
Dx
Lymphoblastic Leukemia in teenager |
T-ALL
|
|
Associated with Acute Promyelocytic Leukemia
(3) |
1) t(15;17)
2) RAR receptor disruption prevents maturation 3) Auer rods cause DIC |
|
Tx
Acute Promyelocytic Leukemia |
ATRA
|
|
Dx
Blasts infiltrate gums, MPO (-) |
Acute Monocytic Leukemia
|
|
Dx
Down sx Leukemia Less than 5 yo More than 5 yo |
Less than 5: Acute Megakaryoblastic Leukemia
More than 5: ALL |
|
Dx
Hypercellular bone marrow with Cytopenia, blasts in bone marrow Less than 20% blasts More than 20% blasts |
Less than 20% blasts = Myelodysplastic sx (from previous chemo/rad)
More than 20% blasts = Leukemia proper |
|
Dx
Neoplasm of naive B cels, CD5 and CD20 |
CLL
|
|
Dx
Smudge cells |
CLL
|
|
Complications of
CLL (3) |
1) Lo Ig
2) AIHA 3) Transformation to Large B Cell Lymphoma |
|
Dx
Neoplasm of mature B cells, TRAP positive |
Hairy Cell Leukemia
|
|
Dx
Splenomegaly of red pulp, dry bone marrow tap, lymphadenopathy is absent |
Hairy Cell Leukemia
TRAP(ped) in Red pulp so not in bone or lymph nodes |
|
Tx
Hairy Cell Leukemia |
2-CDA
|
|
Dx
Lytic bone lesions, rash |
ATLL (Adult T cell leukemia lymphoma)
NOT Multiple myeloma |
|
Complication of Chronic Myeloid proliferative disorders
(3) |
1) Hyperuricemia and gout (high nuclear turnover and degradation --> uric acid)
2) Hypercellular marrow --> Marrow fibrosis 3) Chronic leukemia --> Acute leukemia |
|
Neoplasm in CML
|
ALL myeloid cells, but mostly granulocytes especially Basophils
|
|
Mech of CML
|
BCR-ABL fusion with t(9;22) translocation
|
|
CML progresses to what?
|
AML or ALL
*ALL bc mutation can be in Hematopoetic stem cell not necessarily in myeloblast |
|
How to prove CML over physiologic Leukocytosis
(3) |
1) LAP neg
2) Hi Basophils 3) t(9;22) |
|
Mutation in
Polycythemia vera |
Jak2 kinase mutation
|
|
Dx
Blurry vision, HA, flushed face, itching after shower |
Polycythemia vera
|
|
Neoplasm of Platelets
Neoplasm of Megakaryocytes |
Plts = Essential Thrombocythemia
Megakaryocytes = Myelofibrosis |
|
Which myeloproliferative disorder RARELY progresses?
|
Essential Thrombocythemia (plts don't have nuclear material)
|
|
Dx
Follicle hyperlasia (2) |
1) Rheumatoid arthritis
2) Early HIV infxn |
|
Dx
Sinus histiocytes in lymph node |
Lymph node is draining a cancer (not necessarily metastatic)
|
|
Dx, Etio
Adult, t(14;18) |
Follicular Lymphoma
(a type of Non-Hodgkin's Lymphoma) Bcl2 to Ig Heavy chain |
|
Tx
Follicular lymphoma |
Rituximab (CD20 MAb)
|
|
Dx, Etio
t(11;14) |
Mantle Cell Lymphoma
(a type of Non-Hodgkin's Lymphoma) CDK1 to Ig Heavy chain |
|
Dx
Lyphoma in setting of chronic inflammatory state |
Marginal Zone Lymphoma
(a type of Non-Hodgkin's Lyphoma) |
|
Dx, Etio
t(8;14) Jaw mass - Abdominal mass - |
Burkitt's Lymphoma
c-myc to Ig Heavy chain Jaw = African Abdomen = sporadic |
|
Dx
Neoplasm of B cells making sheets in lymph node or OUTSIDE a lymph node |
Diffuse Large B cell Lymphoma
(a type of Non-Hodgkin's Lymphoma) |
|
Almost All Lymphomas are what cell
|
B cell
|
|
Dx
Hodgkin's Lymphoma 1) Lacunar cells 2) Best prognosis 3) Abundant Eos (IL-5) 4) Worst prognosis (HIV pts) |
1) Nodular scleroris
2) Lymphocyte rich 3) Mixed cellularity 4) Lymphocyte depleted |
|
Dx
High IL-6 in blood |
Multiple Myeloma
|
|
Most common Ig's in MM
|
IgG > IgA
|
|
Dx
Rouleaux formation |
Multiple myeloma
RBC electrical charge of membrane disrupted by Ig's so stack up into rolls of poker chips |
|
Amyloid in Multiple Myeloma
|
Ig Light chain overproduced --> Primary AL amyloidosis
|
|
Dx
High serum monoclonal IgM, LAD, no lytic bone lesions |
Waldenstrom Macroglobulinemia
|
|
Dx
Tennis racket on EM (Birbeck granules) |
Langerhan cell Histiocytosis
|
|
Rules for Langerhans cell Histiocytosis:
(3) |
1) If eponym = malignant = skin rash + bone problems
2) If 2 names, presents in 2 yo or younger 3) If 3 names, 3 yo or older |
|
Dx
Pathologic bone fracture in adolescent, Langerhans cells with Eos on biopsy |
Eosinophilic Granuloma
( a Benign Langerhans Histiocytosis) |
|
What is the other thing Pathoma teaches us helps us discriminate between Megaloblastic and Nonmegaloblastic Macrocytosis?
|
Megaloblastic anemia = Hypersegmented neutros
Nonmegaloblastic = Normal neutros (EtOH, Liver disease, and Reticulocytosis) |
|
HbSC phenotype?
|
Milder than HbSS
|