MF2 HEMATOLOGY Flashcards
Hematopoeisis
Monoblast -> monocyte
Myeloblast -> basophil,
Common -> neutrophil,
Myeloid eosinophil
Promegakaryocyte -> platelets
Preerythroblast -> RBCs
Stem cell ->
Common B-lymphocyte
Lymphoid -> Lymphocyte -> NK Cell
T -> Th & Tc
Basophil, neutrophil, eosinophil = 5-10 days
Platelets = 7-10 days
RBCs = 100-120 days
Pancytopenia
BM SUPPRESSION
- Drugs sequestration
> Chemo
> Radiation
> HIV meds
> Anti-seizure
> Anti-thyroid
> Sulfonamides
- Infection
> Viral (HIV, Hep B, EPV, parvovirus B19)
> Bacterial (TB)
- Illness
> MDS
> Lupus
> DIC
> Starvation, Anorexia nervosa
> Autoimmune destruction
> Aplastic anemia (acquired, inherited)
- Fanconi
> Sarcoidosis
SPLENOMEGALY
Microcytic Anemias
TAILS (thalassemia, anemia chronic disease, Fe, lead, sideroblast)
DECREASED HEME DECREASED GLOBIN
- Fe deficiency
> Sometimes high platelets - Sideroblastic
> High hepcidin, lead
> Buildup Fe RBC in periphery
> Defect ih heme synthesis - Copper deficiency
- Anemia chronic disease
> Hepcidin (liver) response to inflammation
> Feroportin in macros
DECREASED GLOBIN
- Thalassemia
> alpha
- Minima: silent
- Minor: trans v cis
- HbH: moderate, 4B
- Hb Barts: deadly
> beta
- Minor: often silent
- Intermedia: less B
- Major: no B; 3-6 months; anemia, jaundice, hemochromatosis, large forehead, cheekbones
Normocytic Anemia
—- HEMOLYTIC —-
INTRINSIC
- Membrane Issue
> Hereditary spherocytosis (no ankyrin or spectrin)
> Eliptocytosis
> Paroxysmal nocturnal hemoglobinuria (complement
mediated)
- Enzyme issue
> G6DPH anemia (ROS destroy Hb -> Heinz bodies;
common in young African Americans, post infection)
- Folic acid
> Pyruvate kinase deficiency (less ATP –> rigid)
- Hemoglobin Issue
> Sickle cell anemia (B globin point mutation; shape
change when deoxy -> aggregate -> polymers -> lyse->
free Hb -> low haptoglobin -> high unconjugated
bilirubin (jaundice, gallstones) -> increased BM to
compensate & extramedullary hematopoeisis
(hepatomegally) -> VASO-OCCLUSION -> acute chest,
stroke (Moya-Moya), pain crisis, auto-splenectomy,
renal necrosis, priapism, aplastic crisis, marrow infarct
(-> fat emboli);
**Howel-Jolly bodies
**Folic acid, hydroxyurea, supportive care for vaco-occ
> Hemoglobin C disease
EXTRINSIC
- Infection (fever, rash)
> Sepsis
> Malaria
> Babesiosis
> Disseminated C. difficile
- Autoimmune
> Cold ( - IgG, + IgM )
> Warm ( + IgG )
- Microangiopathic hemolytic anemia (MAHA)
> DIC (septic, high coagulation, low fibrinogen)
> TTP (fever, anemia, thrombocytopenia, renal, neuro)
> HUS (younger, prior GI infection, acute renal failure)
> HELLP (pregnant, elevated LFTs; preeclampsia)
> Mechanical valve (chew up RBCs)
—-NON-HEMOLYTIC —-
- Hypothyroidism
- Early Fe deficiency
- Liver failure
- Early B12/Folate deficiency
- Poor gut absorption (low Fe and B12)
- CKD (kidneys make EPO)
- Hemorrhagic (acute blood loss)
Macrocytic Anemia
MEGALOBLASTIC (DNA synthesis issue)
- B12/Folate deficiency (pancytopenia)
- Fanconi aplastic anemia (pancytopenia)
- Orotic aciduria
NON-MEGALOBLASTIC
- Liver disease
- Diamond Blackfam anemia
- Alcohol abuse
Ferritin vs transferrin
Ferritin: Fe storage
> Fe deficiency anemia low
> Anemia chronic disease high
Transferrin: Fe binding
> Fe deficiency anemia high
> Anemia chronic disease low
Hemostasis: regulation
- Secrete NO, PGI2 –| platelets
- Heparin sulfate binds antithrombin III –| II, IX, X
- Thrombomodulin binds II –> protein C –| V, VIII
Hemostasis Steps
- Vascular spasm: endothilin, inflammation -> smooth muscle contraction
- Platelet plug formation: vMF by endothelial cells –> platelets bind via GpIa –> bind eachother by GpIIb/IIIa & fibrinogen –> secrete ADP, thromboxane A2, serotonin –> stimulate platelets & vasocontriction
***Aspirin inhibits TXA2
- Coagulation:
> Extrinsic: III –> VII –> IX
> Intrinsic: XII –> XI –> IX
> Common: Ix + VIII –> X + V –> prothrombin activator
–> II + I –> Fibrin + XIII –> FIBRIN MESH
**Not made by liver: III, VIII
**Shortest half-life: VII
**Longest half-life: II
**Made with vitamin K: X, IX, VII, II (1972)
> Warfarin inhibits VK
- Clot retraction: platelet-derived growth factor (collagen, endo repair)
- Fibrinolysis: plasminogen eats clot
Coagulation Tests
- INR: problem with extrinsic and/or common pathway
(ratio measures time to clot) - aPTT: problem with intrinsic and/or common pathway
(activation partial thromboplastin time) - TCT: activity of fibrinogen (I; thrombin clotting time)
- Factor deficiency vs inhibitor: mix with normal blood
> Corrects: deficiency
> Does not correct: inhibitor (auto-Ab; if delayed often
for VII, VIII b/c delayed activation)
Primary hemostasis vs secondary hemostasis bleeding disorders
PRIMARY
- Instant onset bleeding
- Mucosal bleeding (superficial)
> Nose
> Gums
> Periods
> GI
- Petichae (won’t disappear when you press)
- Vascular or Platelet issue
SECONDARY
- Delayed onset bleeding
- Joint bleeding
- Bleed into muscle -> compartment syndrome (*electrolytes, myoglobin, lactic acid, hyperK)
- Affecting intrinsic, extrinsic, or common pathway
Bleeding disorders
PRIMARY
- Vascular
> Amyloidosis
> HHT/Osler Webber Rendu (bad vessels)
> Ehlers Danlos (bad collagen)
> Scurvy (low vitC → bad collagen)
> Cushings (thin walls)
> Vasculitis, infection - Platelets
> Quantitiative
- Low production: aplastic anemia
- Increased destruction: ITP, TTP/HUS, HIT
- Sequestration: splenomegaly
> Qualitative
- Bernard soulier syndrome (Gp1b deficiency)
- Glanzmans syndrome (GpIIb/IIIa)
- Drugs (ASA, EtOH, NSAIDs)
- Renal failure
- Myeloproliferative disorder
> vWD: most common inherited bleeding disorder
- VIII broken down faster, eventual deficiency
- Type 1: 3/4 cases; mild quantitative defect, non-severe
- Type 2: qualitative, moderate-severe
> A = reduced platelet adhesion b/c multimer
> B = increased GPIb affinity (**don’t use DDAVP)
> M = reduced platelet adhesion
> N = decreased FVIII affinity (recessive)
- Type 3: quantitative, near/total absence, severe (rec)
- Epistaxis, oral cavity bleeding, menorrhagia
- Normal PT, n/low platelet, n/prolonged aPTT, vWD
testing, VIII activity
- TREATMENT: estrogen contraceptives for
mennhoragia, DDAVP for mild (1, 2A); if
active bleeding, surgery desmopressin
(DDAVP), vWF:VIII, antifibrinolytics
(tranexamic acid)
SECONDARY
- Intrinsic
> Hemophilia: X-linked recessive, 50% severe
- Easy bruising, hemarthrosis, epistaxis, hematomas
- Prolonged aPTT, PT/INR, vWF:Ag, platelets normal
- Hemophilia A: VIII deficiency, most common
- Hemophilia B: factor IX deficiency, “Christmas”
- TREATMENT: desmopressin (DDAVP), VIII concentrate,
antifinrinolytics (tranexamic acid)
> vWD
> Factor IX deficiency: common in Ashkenazi Jewish, mild
- Extrinsic
> Factor VII (acquired factor inhibitor; malignancy,
autoimmune disorders, post-partum) - Common
> Vitamin K deficiency (needed for some factors; 1972)
- Drugs: warfarin, antibiotics
- Poor diet
- Biliary obstruction
> Liver disease (makes factors)
- Thrombocytopenia, deficiency in factors (but VIII), less
II, less anticoagulants and altered fibrinolysis
> DIC (use up factors)
Thrombocytopenia
**mucocutaneous bleeding, epistaxis, perioperative bleeding, heavy period, bruising, petichiae, ecchymoses, purpura (non-palpable, wet)
INCREASED DESTRUCTION
- Immune
> ITP
> Viral: HIV
> Systemic: SLE, RA
> Alloimmune
> Drug-induced
- HIT
- Quinine
- Sulfonamides, ampicillin, vancomycin
- Acetaminophen, ibuprofen, naproxen (aleve)
- Non-immune
> HELLP, preeclampsia
> Thrombotic microangiopathies: hemolytic anemia, low
platelets, organ damage from microthrombi
- TTP
- HUS
> DIC
DECREASED PRODUCTION
- B12/Folate deficiency
- Marrow damage
> Chemo, radiation
> Aplastic anemia
> Malignancy
> Myelodysplastic
> Drug-induced
- Valproic acid
- Daptomycin
- Linezolid
> Congenital
- Alport (kidney disease, TPO)
- Fanconi syndrome (kidney disease, TPO)
SEQUESTRATION
- Splenomegaly
> Liver failure
> Portal HTN
> Infection (HIV, mono, Hep C, Tb, endocarditis)
> Amyloidosis, sarcoidosis, hemochromatosis
- Malignancy
> Lymphoma
> Leukemia
HIT
Heparin-induced thrombocytopenia (HIT)
- Type I HIT: also known as heparin-associated thrombocytopenia (HAT), non-immune mediated reaction.
> More common than type II
> Mild reaction, not associated with complications,
platelet counts spontaneously normalize (even if
heparin continued) - Type II HIT: immune, antibody-mediated reaction (PF4-heparin + IgG –> activates more platelets)
> Time for Abs, 5 to 14 days after heparin
> If exposed to heparin w/in 100 days, Abc may remain
> Serious rxn -> hypercoagulable state ->
venous/arterial thrombosis –> DVT, PE, skin necrosis
> Macros eat IgG coated platelets - 4T SCORE
> Thrombocytopenia (30-50% drop)
> Thrombosis (DVT, MI, gangrene, etc)
> Timing (5-14 days)
> Thrombocytopenia (other causes) - ELISA: antibodies test
- SRA: confirm IgG
- TREATMENT
> Stop heparin
> Anti-thrombins: argatroban
> Anti-X: rivoroxaban (take with food!!), apixaban, edoxapan
> If on warfarin, stop and five vitK
TTP
Thrombotic thrombocytopenic purpura (TTP)
- Decreased ADAMTS-13 (cleaves vWF)
- Congenital (5%) or acquired (95%; auto-Abs)
> Congenital: kids
> Acquired: adults; cancer, meds, HIV, BM transplant, SLE - PRESENTATION: Fever, Anemia, Thrombocytopenia, Renal failure, Neurological deficits ; can be mild and non-specific symptoms
- INVESTIGATION: ADAMTS13 activity, inhibitor, platelets, hemolysis (cooms, haptoglobin, LDH), MCV, INR, creatining
- TREATMENT: plasma exchange, corticosteroids, FFP, caplacizumab (prevents platelet vWF interaction, so stop thrombi formation)
Blood film interpretation (size, colour, shape)
SIZE
- Microcytic <80
- Normocytic 80-100
- Macrocytic >100
- Anisocytosis: variability in size
> low Fe, hemolytic, myelofibrosis, myelodysplastic
COLOUR
- Hypochromic: central pallor
> low Fe, anemia chronic disease, sideroblastic
- Polychromasia: increased reticulocytes (pinkish-blue)
> Increased RBC production by BM
SHAPE
- Poikilocytosis: increased proportion of abnormal shape
> Fe low, Hb-opathies, severe low B12, myelofibrosis
**myelofibrosis = bone marrow cancer (uncommon)
**myelodysplastic synromes = cancers where blood cells in the bone marrow do not mature
RBC inclusions
- Nucleus: erythroblast → hemolytic anemia, BM infiltration
- Heinz bodies: Thalassemia, G6PD, unstable Hb
- Howell-Jolly bodies: megaloblastic, hyposplenism
- Basophilic stippling: blue granulations → thalassemia, heavy
metal, megaloblastic, myelodysplastic - Sideroblast: late erythrocyte → drugs, ethanol, hypothyroid,
idiopathic
Hypersegmented neutrophils
> 5 lobes suggests megaloblastic process
- B12 deficiency
- Folate deficiency
Bone marrow aspiration and biopsy
- Posterior iliac crest/spine, sternum (apsiration only)
- Aspiration: takes fluid marrow for cell morphology
- Biopsy: takes intact BM for histology and
immunohistochemistry
Causes of splenomegally
CHINA
Cirrhosis, congestion (portal HTN)
Hematological
> Nutritional anemias
> Hb-opathies
> Hemolysis
> Spherocytosis
> Sequestration crisis
Infectious
> Viral: EBV, HIV
> Bacterial: TB, endocarditis
> Parasitic: malaria, histoplasmosis, leishmaniasis
Neoplasm
> Leukemia
> Lymphoproliferative disease
Autoimmune
> SLE
> Sarcoidosis
Microcytic anemia iron tests (ferritin, serum Fe, TIBC, % sat, RDW)
Ferritin Serum Fe TIBC % sat RDW
Fe deficiency: low low high low high
Chronic disease: n/high low low n n
Sideroblastic: n/high high n n/high high
Thalassemia: n/high n/high n n/high n/h
Organs affected by vaso-occlusive crisis
Brain = ischemic or hemorrhagic stroke
Eye = hemorrhage, blindness
Liver = infarcts
Lung = acute chest syndrome, long-term pulmonary HTN
Gallbladder = stones
Heart = hyperdynamic flow murmurs
Spleen = enlarged (child), atrophied (adult)
Kidney = hematuria, proteinuria
Intestines = acute abdomen
Placenta = stillbirths
Penis = priapism
Digits = dactylitis
Bone = infarction, infection, avascular necrosis
Skin = leg ulcers (ankle)
Drugs associated with thrombocytopenia
trimethoprim/sulfamethoxazole
heaprin
NSAIDs
Vancomycin
Digoxin (increased myocardial contractility, reduce HR)
Acetominaphen
Ethanol
H2-antagonists (for duodenal ulcers)
Thrombocytopenia treatment
EMERGENCY
- Corticosteroids (prednisone)
- Antifibrinolytic if mucosal bleeding
- Platelet transfusion for major bleeding or urgent surgery
NON-URGENT
- 1st line: corticosteroids
- 2nd line: splenectomy, rituximab
- 3rd line: TPO receptor agonsist
Affects of alcohol on hemostasis
- Harm liver → TPO synthesis
- Bone marrow suppression
- Decrease lifespan of platelet
- Directly toxic to platelets in blood
- Impair platelet response to activators
- Rebound effect: acute platelet drop when drinking then
when stop → thrombocytosis → can lead to stroke
