Blood

Front 1

Hematopoietic Stem Cell phenotype: HIGH quality HSCs
CD34:
Size:
Lin:
ALDH:
HLA-DR:
Hoecst SP:

Back 1

High quality HSC
CD34: +/-
Size: Small lymphocyte
Lin: -
ALDH: ++
HLA-DR: low
Hoecst SP:neg

Front 2

Hematopoietic Stem Cell phenotype: LOW quality HSCs
CD34:
Size:
Lin:
ALDH:
HLA-DR:
Hoecst SP:

Back 2

Low quality HSC
CD34:+
Size:blast (larger)
Lin:-/+
ALDH:+/low
HLA-DR: +
Hoecst SP:+

Front 3

Anemia Hb normal levels
Anemia hematocrit normal levels

Back 3

<14 gm/dl in men, 12 gm/dl in women, 11 gm/dl in pregnant women.
30-50% hematocrit.

Front 4

Common hypochromic, microcytic anemias

Back 4

Iron deficiency
Thalassemia syndromes
Sideroblastic anemia
Transferrin deficiencies

Front 5

Common macrocytic anemias

Back 5

Megaloblastic anemias (folic acid/B12 deficiencies)
Liver disease
Reticulocytosis
Normal newborns
Bone marrow failure
Drugs (AZT, TMP-SMX)

Front 6

Normocytic, normal morphology

Back 6

Hemorrhage or blood loss, unstable hemoglobins, infections, chronic disease.

Front 7

Differences between B12 and Folate deficiencies

Back 7

Folate deficiency is usually dietary.
B12 is in animal products, Folate in liver and leafy greens.
Only B12 increases methylamlonic acid.
B12 is absorbed in the terminal ileum and requires intrinsic factor.

Front 8

Markers for intravascular hemolysis:

Back 8

*Lower hemopexin*
High plasma hemoglobin
Hemoglobinuria/hemosiderinuria
Methemealbumemia

Front 9

Types of hemoglobin:

Back 9

Adult: HbA (a2B2)
Other adult: HbA2 (a2d2)
Fetal: HbF (a2g2) <--increase with hydroxyurea.

Front 10

B and a thalessemia

Back 10

In Beta-thalessemia there's a selective survival of the minor Hb's because they don't need a Beta subunit.
Alpha-thalessemia is often confused with iron deficiency (microcytic RBCs), and there is no relative increase in minor Hb's.

Front 11

Factors released by and affecting platelets

Back 11

As adhesion occurs platelets are activated and release ADP and thromboxane, which recruits other platelets. End product of the CC (thrombin) recruits even more platelets, and converts fibrinogen to fibrin.

NO and PGI2 from endothelium inhibit platelets.

Front 12

Coagulation cascade

Back 12

Intrinsic pathway: XII-->XI-->IX-->VIII
Extrinsic pathway: VII + Tissue factor
Common pathway: X-->V-->II
II (prothrombin) activates fibrinogen, V, VIII, XIII and platelets.

Front 13

Serine proteases:
Cofactors:
Vitamin K-dependent factors:

Back 13

Serine proteases: 12,11,10,9,7,2
Cofactors: VIII and V
Vitamin K-dependent factors:10,9,7,2, C, S.

Front 14

Clotting tests
aPTT:
PT:

Back 14

aPTT: Tests intrinsic and common pathways. Only needs plasma with added phospholipids, calcium, and XII activator (to start intrinsic pathway).
PT: Tests extrinsic (VII) and common pathway. Uses serum with phospholipids, calcium and tissue factor.

Front 15

Endogenous anti-thrombin proteins.

Back 15

Antithrombin (III): Disposes of X and II in common path. Made by liver. *Acts faster with heparin*
Thrombomodulin: Deactivates thrombin away from site of injury.
Protein C and Protein S downregulate VIII and V on surface of platelets. Estrogens raise C4b binding protein levels, and C4b inactivates Protein S.

Front 16

Aspirin

Back 16

Mechanism: Inhibits cyclooxygenase to block production of thromboxane A2-->inhibition of aggregation, and vasodilation.
MEC for these effects (160mg) much lower than for inflammation/fever.

Front 17

Dipyridamole

Back 17

Mechanism: Increases intracellular cAMP by inhibiting cyclic nucleotide PDE.
Inhibits nucleoside transport/uptake-->more cAMP signaling-->inhibits aggregation, and vasodilates. Only useful with warfarin or aspirin!

Front 18

Ticlopidine and clopidogrel

Back 18

Mechanism: Inhibit ADP-induced platelet aggregation.
Block ADP-mediated release of lpatelet granules, inhibits fibrinogen binding.
Side effects: Inhibits P450's. Neutropenia, bleeding, diarrhea. Clopidogrel's better than ticlopidine.

Front 19

IIb-IIIa receptor antagonists.
One antibody
One peptide
One small molecule

Back 19

Mechanism: The IIb/IIIa receptor crosslinks and activates platelet aggregation, so all these drugs block aggregation.
Antibody coats the receptor, potential for serum sickness.
Peptide blocks fibrinogen, vWf, vitronectin from binding to the receptor.
Small molecule does same stuff.

Front 20

Erythropoietin

Back 20

Mechanism: Activates Jak-STAT pathway, which blocks apoptosis of precursor cells.
Clinical uses: Anemia of chronic renal failure (b/c EPO's made there).
Toxicity: Theoretical risk of neoplasm (b/c it's a TK activator).

Front 21

Heparin

Back 21

Mehcanism: Enhances activity of antithrombin (intrinsic pathway, X and II).
Pharmacokinetics: Dosed in units of activity.
Toxicity: Thromboycytopenia, alopecia, osteoporosis.
Reversal of activity: Monitor with aPTT. Stop therapy or give protamine, which binds heparin. Give fresh frozen plasma.

Front 22

Molecular weight heparin

Back 22

Mechanism: Inhibits X but NOT II (as heparin does).
Pharmacokinetics: Increased bioavailability and longer plasma t1/2 than heparin.
More expensive than heparin, but doesn't require therapeutic monitoring.

Front 23

Warfarin

Back 23

Mechanism of action: Vitamin K antagonist in post-translational processing of 10, 9, 7, 2, C, S.
Pharmacokinetics: II has the longest t1/2, so it takes the lonest to be affected.
Use PT to monitor effect (VII, extrinsic).
Toxicities: Warfarin can actually cause a hypercoagulable state. Treat with FFP and Vitamin K. Teratogenicity!
Drug interactions: LOTS. Enhances some oral anticoagulants, inhibits and inhibited by others.

Front 24

Streptokinase:
Urokinase:
Recombinant tissue plasminogen activator:

Back 24

All thrombolytics.
Streptokinase: Allosteric regulator of plasminogen. Activates plasminogen to break down clots.
Urokinase:Cleaves plasminogen directly, like tPA. Can induce systemic fibrinolysis.
Recombinant tissue plasminogen activator: Binds extra avidly to fibrin-bound plasminogen and activates it.
Toxicities: Bleeding for all, allergic reactions for strep- and urokinase.

Front 25

Procoagulant drugs:

Back 25

E-Aminocaproic acid: Analogue of lysine, competitively inhibits binding of plasmin to fibrin.
Desmopressin: Analogue of vasopressin/ADH, acts to release VIII and vWF. Used in mild hemophilia.

Front 26

Multiple Myeloma (a plasma cell dyscrasia)

Back 26

Excessive globulin secretion in blood/urine, normally light chains. IgG common.
Neoplastic proliferation of a plasma cell, often evolved from MGUS.
Use PEP to detect M-protein spike, then IFE to specify.
Need at least one of BIRRA HA evidence of end organ damage.
10% of blood cancers, typically in old age.

Front 27

Chronic Myelogenous Leukemia

Back 27

Many small megakaryocytes.
Splenomegaly usually present, lymphadenopathy uncommon.
5-6 years chronic phase then 1 year accelerated and blast crisis.
Fusion between abl on chromosome 9 and bcr on 22.
Stem cell neoplasm with mature elements predominating.
Indolent disease of adults.

Front 28

Chronic Lymphocytic Leukemia

Back 28

Neoplasm of mature cells, not stem cells.
Commonest leukemia in Western world.
Cytopenias, infections, transformation to aggressive lymphoma.

Front 29

Acute Myeloid Leukemia

Back 29

Blasts rather than mature cells. Proliferative advantage rather than anti-apoptotic of chronic leukemias.
Mature elements of all lineages are decreased.
Rapidly fatal if left untreated, but many patients will remiss. MDS genetic lesion is a bad one...
Death comes from infections/bleeding.
Myeloperoxidase and myeloid surface markers. Auer rods!

Front 30

Acute lymphoid leukemia

Back 30

Most common tumor of childhood (80% of childhood leukemia).
Presenting characteristics are same as ALL.
Usually B-precursor, can be T though.
More than 3/4 of kids can be completely cured.
TdT marker.

Front 31

Hematolymphoid immunology

Back 31

All lymphoid cells have CD45 except for classical hodgkins.
Follicular B cells have CD20, sIg.
Paracortical T cells have CD3 and CD4 or CD8.
Sinus histiocytes have CD68.
Malignant hodgkin lymphoma have CD15 and CD30.

Front 32

Hodgkin Lymphoma

Back 32

B cell origin. Characterized by Reed-sternberg cells (binucleated, eosinophilic) and immunoreactive reponse of eosinophils, plasma cells, and small lymphocytes.
Bimodal age distribution.
Low stage, non-extranodal disease common, prognosis excellent. NSHL seen in mediastinum of young women.

Front 33

Non-hodgkin lymphoma

Back 33

B or T cell origin. Commonly extranodal. Generally older patients except lymphoblastic and Burkitt's.
"Low grade" lymphomas are mature differentiated lymphocytes like, like chronic leukemia. Rare in children. Includes follicular lymphomas (bcl-2), mantle cell lymphoma, MALT lymphomas, and Indolent T cell lymphomas (rare).
"High grade" lymphomas are immature or activated (like ALL and AML). Lymphoblastic lymphoma (only one common in kids, often from T cells), diffuse Large B cell lymphoma, Burkitt lymphoma, and rare T cell lymphomas.

Front 34

"Low grade" lymphoma immunophenotyping.

Back 34

Most are CD-20 bright.
Follicular lymphoma: *CD10*
Small lymphocytic lymphoma: CD-20 dim, CD23
Mantle cell lymphoma: cyclin D1.
MALT lymphoma: Only has CD20-bright.