DISORDERS OF HEMOSTATIS

Heparin is released from what 2 types of cells?

What does it combine with and supress to prevent coagulation?

Heparin is released from basophils and mast cells

Prevents blood coagulation by combining with anti-thrombin III cofactor to supress the fibrin formation.

t-PA (tissue plaminogen activator), Streptokinase, and Urokinase are what type of drugs?

When are they used?

Thrombolytic drugs

used to tx MI**, DVT, CVA**

** small window (<3hrs) to tx with drugs

must determine if CVA is hemorrhagic vs. ischemic before administering drugs

A pt presents with mild vascular purpura confined to the skin and mucous membranes (bleeding gums).  What vitamin deficiency do you suspect?

Vitamin C

ascorbic acid deficiency impairs collagen synthesis and will result in extravascular connective tissue deficiencies.

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Hereditary hemorrhagic telanglesctasia (HHT) is an autosomal dominant disorder that is typically identified by the triad of telanglestasia (what is this!?), recurrent epistaxis, and a + FH for the disorder?

What is another name for this disorder and how does it contibute to abnormal bleeding?

Weber-Osler-Rendu Syndrome

formation of abnormal blood vessels

telanglestasia are small dilated blood vessels near the surface of the skin or mucous membrane

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Close-up view of typical symptoms of patient with Osler-Weber-Rendu syndrome with red nodules and starry telangiectasia on the lips.

what is the difference between QUANTITATIVE and QUALITATIVE platelet disorders?  Give examples of each

Quantitative (2)

Qualitative (4)

Quantitative Platelet Disorders:

Decreased Production:  bone marrow failure, chemotherapy, nutritional

Increased Destruction: Immune Thrombocytopenic Purpura (ITP), Auto-immune, Drugs (Heparin)

Qualitative Platelet Disorders:

Abnormal function:  too many platelets but not functioning properly

von Willebrand's

Drugs: ASA, NSAIDs

Metabolic:  uremia, liver failure

give the follwing ranges for platelets:

Normal range:

Bleeding begins to prolong:

Petechiae & purpura:

More serious bleeding:

Spontaneous bleeding:

give the follwing ranges for platelets:

Normal range:  150,00 - 450,000

Bleeding begins to prolong: 100,000

Petechiae & purpura: 20,000 - 50,000

More serious bleeding: < 20,000

Spontaneous bleeding: < 10,000

what condition is most common in younger women (20-40) and is cx by immune mediated thrombocytopenia resulting in accelerate platelet clearance?

What are the 3 causes?

What will a spinal tap show?

Idiopathic/Immune Thrombocytopenic Purpura (ITP)

3 causes:

Viral illness (including HIV)

drugs

vasculitis (lupus)

Spinal Tap:

normal or increased # of megakaryocytes in bone marrow

The megakaryocyte is a bone marrow cell responsible for the production of blood thrombocytes (platelets).

von Willedrand's disease, ADA, NSAIDs, uremia, or liver failure are ____________ causes of platelet dysfunction, otherwise known as thrombocytopathia.

thrombocytopathia = abnormal platelet function due to abnormal adherence and/or adhesion

von Willedrand's disease, ADA, NSAIDs, uremia, or liver failure are QUALITATIVE causes of platelet dysfunction, otherwise known as thrombocytopathia.

thrombocytopathia = abnormal platelet function due to abnormal adherence and/or adhesion

what is the most common inherited bleeding disorder?

What does this disease cause?

von Willebrand's Disease

causes a defect in platelet adherence due to depressed vWF (glycoprotein) levels, which functions to bridge platelets to exposed collagen at the site of vascular injury.

A pt presents with abnormal bleeding involving the skin and mucous membranes (immediate mucocutaneous bleeding or delayed deep tissue bleeding post trauma) with petechia, purpura, and seeping bleeds.  Labs show prolonged PTT, decreased vWF levels, and abnormal platelet aggregation study.

What is your dx?

What coagulant factor is possibly decreased?

von Willebrand's Disease

Factor VIII coagulation factor possibly decreased

 replacement of Factor VIII

Desmopressin acetate

cryoprecipitate

tx for what?

Which of the coagulation factors are synthesized by the liver and require vitamin K as a cofactor in the final stage?

what cofactor is not made in the liver?

Factors II, VII, IX, X

2 + 7 = 9 + 1 = 10

Factor XIII not made in the liver

How does liver disease affect blood clotting? 

synthesis and clearance...

Liver Disease

Impaired synthesis of Vitamin K dependent clotting proteins, fibrinogen, and plasminogen

Impaired clearance of FDP (fibrin degredation production) and activated coagulation factors

Portal HTN → splenomegaly and excessive platelet pooling

Disseminated Intravascular Coagulapathy (DIC)

VERY HIGH MORTALITY

DIC

What labs are consistent with DIC:

PT/PTT:

Fibrinogen:

FDP, D-Dimer:

Labs consistent with DIC:

PT/PTT:  PROLONGED

Fibrinogen:  LOW

FDP, D-Dimer: HIGH

what bleeding disorder is transmitted on the X chromosome and is manifested in males?

What are the types of this disorder and the corresponding Factor deficiencies

Hemophilia

Hemophilia A -- Factor VIII deficiency

Hemophilia B (Christmas Disease) -- Factor IX deficiency

a young male presents to the office with bleeding into joints following a fall.  Lab tests show prolonged PTT with normal PT, fibrinogen, and bleeding time. 

What do you suspect as the Dx and how would you confirm you Dx?

Hemophilia A  (Factor VIII Deficiency)

Dx is made by factor assay showing a decrease in Factor VIII:C

deep tissue bleeding, hematomas, bleeding into the CNS, peritoneum, GI tract, and retroperitoneum are cx of what disease?

Which type of acute bleed is very painful and may cause temporary immobility?

Hemophilia

Acute joint bleeds are very painful and may cause temporary immobility

PT - Prothrombin Time - Warfarin tx

results reported in INR

PTT - Partial Thromboplastin Time - unfractionated heparin tx and hemophilias

what lab test analyzes clotting ability of plasma coagulation factors PT, fibrinogen, and Factors V, VII, and X?

what is the test measuring?

PT - Prothrombin Time

test is measuring the # of seconds for blood to clot when mixed with a thromboplastin reagent

REPORTED IN INR

The 5 mechanisms of Hemostasis

1. vessel spasm
2. formation of platelet plug
3. blood clot formation -- development of insoluble fibrin
4. clot retraction and fibrous tissue growth -- permanent repair of vessel injury
5. clot dissolution

ANEMIAS

what a lab test is used to evaluate anemia for which we need to know the values for men and women?

Lab test = Hgb (Hemoglobin)

Anemia in women Hgb < 12

Anemia in men Hgb <13

A deficiency in ________ will cause anemia due to a decreased RBC production.

A deficiency in _____(2)___  will cause anemia due to decreased in RBC maturation.

A deficiency in Fe (iron) will cause anemia due to a decreased RBC production.

A deficiency in B12, Folic Acid  will cause anemia due to decreased in RBC maturation.

Ferritin is involved in the ____________

**ferritin the most senstive test for what condition?

Transferrin is involved in the _____________ and is produced by the __________

TIBC (?) an indirect measurement of _____________

Ferritin is involved in the storage of iron

**ferritin the most senstive test for what iron deficiency anemia

Transferrin is involved in the tranport of iron and is produced by the liver

TIBC (total iron binding capacity) is an indirect measurement of transferrin and is used to with serum iron to calculate percent transferrin saturation (serum iron / TIBC x 100)

MCV, MCHC, and MCH meaure _________ of _________.

MCV is used to determine what? (3)

MCV, MCHC, and MCH meaure volume of RBCs.

**MCHC--giving the amount of hemoglobin per volume of erythrocytes

**MCH--the amount of hemoglobin per cell

MCV is used to determine if an anemia is classified as:

microcytic (MCV below normal range)

normocytic (MCV within normal range)

macrocytic (MCV above normal range).

when reticulocyte count is normal or low in the presence of anemia, ____________ of RBC is the problem and MCV will help distinguish the cause.

the bone marrow response to anemia due to blood loss or hemolysis will lead to what?

the bone marrow response to anemia due to blood loss or hemolysis will lead to increased production of reticulocytes (large, immature RBCs)

Give the MCV value, common cause, and less common cause for the following morphologic classifications of anemia:

_________________is the most common form of anemia and is an anemia due to low __________.

What are the top causes in poor countries? (2)

Top causes in developed countries? (2)

Iron deficiency is the most common form of anemia and is an anemia due to low production.

What are the top causes in poor countries?

nutritional deficiencies

parasite infections

Top causes in developed countries?

GI blood loss

menometrorrhagia

pregnancy and childhood growth can lead to what type of anemia?  due to what?

how do GI resection, malabsorption, IBD, and poverty lead to this type of anemia?

pregnancy and childhood growth can lead to iron deficiency anemia due to increased use of iron 

GI resection, malabsorption, IBD, and poverty lead to iron deficiency anemia due to decreased input/uptake of iron

If your labs came back with the following results, what type of anemia would you suspect?

CBC:  low RBC count, Hb, Ht

Blood smear:  pale, small RBC

Low ferritin, Fe, TIBC high

What is the treatment (generally)?

Iron deficiency anemia (IDA)

Treatment:

IDENTIFY THE CAUSE OF THE Fe DEFICIENCY

replace iron + Vit C (improves absorption)

improve diet

F/U in 3-4 months and check retic count

retic count should increase in 10-14 days towards normal values

what are the causes of vitamin B12 deficiency? (4)

Vitamin B12 deficiency:

inadequate intake (rare):  veganism

inadequate absorption:  lack of INF (autoimmune, celiac disease, malignancy

inadequate utilization:  malignancy

increased requirements:  hyperthyroidism, infancy, parasitic infection

chronic alcoholism causes what type of anemia?  due to what?

megaloblastic anemia (HIGH MCV)

phenytoin, oral contraceptives interfere with folic acid absorption

methotrexate, anticonvulsants decrease utilization of folic acid

what are the causes of anemia due to decreased production?

(5)

decreased production:

iron deficiency hypochromic, microcytic

folate deficiency  macrocytic

Vit B12 deficiency macrocytic

bone marrow problems (aplastic anemia & pancytopenia)  normocytic

renal failure (loss of EPO)  normocytic

↑ ferritin

↓ TIBC

what type of anemia?

↓ ferritin

 ↑ TIBC

what type of anemia?

LABS:

CBC: ↓ RBC, ↓ HB, ↓ Ht

Retic <2 or nl

MCV < 80

MCHC < 32 (microcytic, hypochromic)

Blood smear: pale, small RBC, anisopoikilocytosis

Fe LOW

Ferritin LOW

TIBC HIGH

type of anemia?

LABS:

Retic < 2

MCV > 95 HIGH

hypersegmentation of PMNs

cause of anemia?

what if the pt also had paresthesias?

folate or vitamin B12 deficiency

paresthesias = vit. B12 deficiency

on blood smear you see RBCs with dark spots in the pale center (target cells).

What's the Dx?

LABS:

↑indirect bilirubin (jaundice)

↓ free haptoglobin

↑ LDH

↑ reticulocyte count

blood smear: fragmented RBCs

Dx?

PT assesses the _________ pathway (Factor?)

PTT assess the __________ pathway (Factors?)

PT assesses the extrtinsic pathway (Factor VII)

PTT assess the intrinsic pathway (Factors XII, XI, IX, VIII)

Hematology/Oncology Testing

_______________= RBC of unequal size

_____________ = abnormally shaped RBCs

anisocytosis = RBC of unequal size

poikilocytosis = abnormally shaped RBCs

what is the normal ratio of

RBC: WBC : Plt

RBC : WBC : Plt

500 :   1  :  30

what type of cell will increase in a bacterial infection?

viral infection?

bacterial = PMN

viral = lymphocytosis

_____________ are proliferations of WBC in the bone marrow

_____________ are proliferations of WBC in the lymphatic tissue

leukenias are proliferations of WBC in the bone marrow

lymphomas are proliferations of WBC in the lymphatic tissue

Myelogenous lineage:

granulocytes (neutrophils, basophils, eosinophils, monocytes)

erythrocytes

plateletes

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B cells

T cells

Natural Killer Cells

[image]

what is an indirect measure of hematopoiesis?

what is a direct measure?

Reticulocyte count

Normal = 0.5 - 1.5 % of total RBCs

direct = bone marrow smear

serum Ferritin

when iron stores increase (as in anermia of chronic disease), ferritin level increases and TIBC decreases

what test is used to evaluate lack of intrinsic factor (Pernicious anemia)?