Pathoma Ch. 4 - Blood Flashcards by Andrew Herrmann

4 steps of primary hemostasis (w/ molecular causes)

Vasoconstriction (reflex neural stim., ENDOTHELIN)
Platelet adhesion (Collagen + vWF + Gp1b)
Degranulation (ADP, TxA2)
Aggregation (2b/3a + fibrinogen)

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Functions of ADP and TxA2 from platelet degranulation

ADP – promote exposure of 2b/3a receptor

TxA2 – promote aggregation

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Petechiae = ____ (NOT ___)

Thrombocytopenia (NOT qualitative disorder)

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Purpose of giving IVIg

Compete with the actual problematic antibodies for the splenic macrophages –> reduce splenic hemolysis

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ITP - where do antibodies come from?

Plasma cells in the spleen

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TTP - why is ADAMTS13 deficient?

Acquired autoimmune antibody to it

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HUS - why the symptoms? (3)

Verotoxin (Shiga-like toxin) causes endothelial cell damage –> thrombus formation in the kidney small vessels

Thrombi –> consumes platelets –> petechiae

Thrombi –> mechanical destruction of RBCs –> hemolytic anemia + schistocytes

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TTP - why the neuro symptoms?

Thrombi form in small vessels of brain

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Treatment for HUS and TTP

Plasmapheresis (remove antibodies)

Corticosteroids (stop antibody synthesis)

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Qualitative platelet disorder + enlarged platelets

Bernard-Soulier (“Big Suckers”)

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How does uremia affect platelet function?

Disrupts adhesion AND aggregation

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Function of the coagulation cascade

What happens after that?

Produce thrombin, which converts fibrinogen to fibrin in the platelet plug

Fibrin is cross-linked –> STABLE

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How to tell if clotting factor is deficient or being destroyed by antibodies?

Deficient –> mixing study corrects it

Antibodies –> mixing study does NOT correct it

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Epoxide reductase

Activator of Vitamin K in the liver

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Function of Vitamin K

What does that mean?

Gamma-carboxylation of factors 2, 7, 9, 10, C and S

Allows for CALCIUM to bind

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Hemorrhagic disease of the newborn

Vitamin K deficiency (no gut bacteria)

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Effect of liver failure on coagulation is measured via ___

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Function of Protein C
Function of Protein S
Function of Antithrombin 3

C = inhibit 5 and 8
S = activate C (w/ thrombomodulin)
AT3 = inhibit 10 and 2 (thrombin)

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HIT…explain

What to watch for?

What NOT to give? Why?

Heparin binds to PF4 on platelets
The body creates antibodies against these complexes
The spleen destroys the complexes (thrombocytopenia)

Platelet bits into circulation –> activation of others –> THROMBOSIS

Warfarin (risk of warfarin skin necrosis)

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Warfarin skin necrosis…explain

Tie in w/ HIT?

Warfarin –> decreased Protein C and factor 7 FIRST –> increased coaguability –> blood clots in skin vessels

HIT –> thrombosis risk –> Warfarin INCREASES thrombosis risk –> tissue necrosis

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Rattlesnake bite –> starts bleeding

Venom –> activates clotting cascade –> DIC

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Sepsis –> bleeding from everywhere

Endotoxin + TNF/IL-1 –> endothelial cells express tissue factor –> DIC

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Obstetric complication –> bleeding from everywhere

Tissue thromboplastin in the amniotic fluid

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D-dimer comes from where?

Splitting of CROSS-LINKED fibrin

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Functions of plasmin What inactivates it?

1. Cleave fibrin 2. Destroy serum fibrinogen 3. Block platelet aggregation Alpha-2 anti-plasmin (serum protease inhibitor)

Radical prostatectomy --> excess bleediing

Release of UROKINASE activates plasmin

``` Bleeding everywhere Increased PT/PTT Increased bleeding time Normal platelet count Normal qualitative studies No D-dimer ``` Treatment?

Plasmin overactivation (cirrhosis, prostatectomy) Tx = Aminocaproic acid (blocks plasminogen activation)

Lines of Zahn Other way to distinguish from post-mortem clot

Alternation of platelets/fibrin w/ RBCs Attachment to vessel wall

Anti-thrombotic functions of endothelial cells (5)

1. Block exposure to collagen and tissue factor 2. PGI2 and NO --> vasodilation and inhibited aggregation 3. Heparin-like molecules --> enhanced AT3 4. tPA 5. Thrombomodulin

Describe the interaction between folate, B12, and homocysteine Why is this important? (the homocysteine part)

- THF circulates as methyl-THF - Methyl transferred to B12 --> THF drives thymidylate synthase (dTMP production) - Methyl transferred to homocysteine --> converted to methionine Elevated homocysteine = THROMBOSIS via endothelial cell damage

Long, slender fingers, lens dislocation, mental retardation, vessel thrombosis Explain

Homocysteinuria CBS deficiency (or B6 deficiency)

Prothrombin 20210A

Inherited point mutation in prothrombin --> increased gene expression --> increased coagulation

OCP hypercoaguability

Estrogen --> increased coagulation factor production

Laparascopic surgery --> respiratory distress

Gas embolus (air pumped into abdomen)

Amniotic fluid embolus -- finding?

Squamous cells and keratin debris in the embolus

What is required for a PE to cause symptoms?

Infarction of large or medium artery + pre-existing cardiopulmonary compromise (usually)

PE -- pathology

Hemorrhagic, wedge-shaped infarct

Microcytic anemias (4)

``` Iron deficiency Anemia of chronic disease (functional deficit of iron) Sideroblastic anemia (deficit of protoporphyrin) Thalassemia (deficit of globin) ```

Absorption location of... - Iron - Folate - B12

``` Iron = duodenum Folate = jejunum B12 = ileum ```

Gastrectomy --> iron deficiency

Acid keeps iron in 2+ state ("goes 2 the blood")

Functions of hepcidin (2)

- Sequester iron, limiting transfer to RBCs | - Suppress EPO

Increased free erythrocyte protoporphyrin

Iron deficiency of some kind

Alpha vs. Beta thalassemia -- genetics

``` Alpha = gene DELETION Beta = gene MUTATION (promotor or splice site) ```

Microcytic, hypochromic RBCs Increased RBC count Target cells Increased HbA2 and HbF What causes target cells? (in general) (2)

Beta-thalassemia minor Decreased cytoplasm OR increased membrane

Microcytic, hypochromic anemia as an infant Crewcut x-ray Chipmunk facies HSM Increased risk for what? (2)

Beta-thalassemia major ``` Infusion-induced hemochromatosis Aplastic crisis (B19) ```

Beta-thalassemia major -- see what on blood smear

Target cells | Nucleated RBCs

Beta-thalassemia major - Hb type(s)?

Increased HbA2 and HbF

Macrocytic anemia w/o megaloblastic change (3)

- Alcoholism - Liver disease - 5-FU (ex.)

Folate vs. B12 deficiency - time frame

Folate - months | B12 - years

Causes of folate deficiency (6)

- Alcoholic (poor diet) - Elderly (poor diet) - Pregnancy (demand) - Cancer (demand) - Hemolytic anemia (demand) - Methotrexate (inhibition)

Describe pathway of B12 absorption (5)

- Amylase liberates it - Bound by R-binder - Proteases in duodenum detach it - B12 binds IF in small bowel - B12-IF complex absorbed in terminal ileum

Causes of B12 deficiency (5)

- Pernicious anemia - Pancreatic insufficiency (no protease to detach it) - Crohn's disease (ileum damage) - D. latum (ileum damage) - Vegans (dietary)

Larger RBCs with bluish cytoplasm

Reticulocytes (residual RNA)

How to determine true reticulocyte count? Why? What do the results mean?

RC x Hct/45 Anemia --> FALSE increased reticulocyte value 3+% = good marrow response (destruction) Under 3+ = poor marrow response (underproduction)

Normocytic anemia + extravascular hemolysis (3)

Hereditary spherocytosis Sickle cell anemia Hemoglobin C

Normocytic anemia + intravascular hemolysis (5)

``` PNH G6PD deficiency Immune hemolytic anemia Microangiopathic hemolytic anemia Malaria ```

Sickle cell - increased risk of sickling (3)

Acidosis Dehydration Hypoxemia

Intravascular hemolysis in sickle cell See what on blood smear?

Damaged membrane due to sickling --> DEHYDRATES --> hemolysis, decreased haptoglobin, etc. TARGET CELLS (dehydration)

Sickle cell + gross hematuria and proteinuria

Renal papillary necrosis

Microscopic hematuria, some HbS found

Sickle cell trait (only sickles in renal medulla)

Metabisulfite test

Any amount of HbS --> sickling | Positive in the disease OR the trait

Hemoglobin C - cause See what on blood smear?

Glu --> Lys mutation (causes MORE positive charge) HbC crystals

PNH - deficiencies

No GPI --> no DAF --> no inhibitor of C3 convertase

PNH - 3 tests for diagnosis

- Sucrose test - Acidified serum test - Flow cytometry for CD55 (DAF)

Death in PNH

Thrombosis of hepatic, portal, or cerebral veins

**2 complications of PNH

- Iron deficiency anemia (chronic hemolysis) | - ***AML

Causes of IgG immune hemolytic anemia (5)

SLE, CLL, Penicillin, Cephalosporins, Alpha-methyldopa

Causes of IgM immune hemolytic anemia (2)

Mycoplasma, Infectious Mononucleosis

IgG vs. IgM immune hemolytic anemia -- hemolysis

``` IgG = extravascular IgM = intravascular ```

Pathoma Ch. 4 - Blood Flashcards

(69 cards)