HEMA: Bleeding Disorder

localized hemorrhage

examples:

• inadequately cauterized

• ineffectively sutured surgical site

• arteriovenous malformation (does not imply blood vessel defect)

bleeding from single location usually indicates injury, infection, tumor, or an isolated blood vessel clot

3 Examples:

• seldom implies blood vessels defect, except for ______

generalized or systemic hemorrhage

multiple sites or systemic

problems with platelet and clotting factors

spontaneous and recurring bleeding

requires medical or physical intervention

mucocutaneous hemorrhage (generalized)

in skin or at body orifices

affects primary hemostasis

may appear

• petechiae (1mm, red pinpoint spots)

• purpura (3mm, purple skin lesions)

• ecchymoses (>1cm, bruises) = damage in blood vessel

other symptoms:

• hematemesis (vomiting of blood)

• epistaxis

• gingival bleeding

• menorrhagia (profuse menstrual flow)

• blood in urine or stool

• thrombocytopenia

• qualitative platelet disorder

• von Willebrand disease

• vascular disorders (scurvy, telangiectasia)

mucocutaneous hemorrhage is most likely to be associated with

anatomic hemorrhage (generalized)

in soft tissue, muscles, joints, deep tissue, organs

seen in acquired or congenital defects in secondary hemostasis

• recurrent or excessive bleeding after minor trauma

• dental extraction

• surgical procedure

• internal bleeding

thorough patient history and physical examination

distinguish between mucocutaneous and anatomic hemorrhage

cause symptoms related to organ affected

cause headaches, confusion, seizures, and coma

may present hematuria and may be associated with acute renal failure

bleeding in body cavities …

bleeding into CNS …

bleeding into kidneys …

1. hgb, hct, retics count

2. plt count

3. Prothrombin time

4. Partial thromboplastin time

5. thrombin time

6. fibrinogen assay

primary assays for generalized hemostatic disorder

thrombin timefi

assay prolonged by unfractionated heparin therapy, dysfibrinogenemia, hypofibrinogenemia, and afibrinogenemia

qualitative result

fibrinogen assay

assay reduced in dysfibrinogenemia, hypofibrinogenemia, and afibrinogenemia

quantitative result

congenital bleeding disorder

ACQUIRED OR CONGENITAL. recurrent hemorrhages may be spontaneous

trauma-induced coagulopathy

triggered by combination of injury-related acute inflammation, hypothermia, acidosis, and hypoperfusion (all elements of systemic shock)

needs surgical procedures to stop and control bleeding

accounts for most instances of fatal hemorrhage (can be prevented through coagulopathy management)

thrombocytopenic purpura

acute reduction of ADAMTS13 (vWF cleaving protease)

tissue factor release, coagulation factor activation, loss of coagulation control proteins, hyperfibrinolysis

systemic shock leads to ______

severe bleeding

low bp, hgb, hct, heart rate

coagulopathy

single or multiple coagulation factor or platelet deficiency

stop bleeding

need blood transfusion (apheresis, avoid transfusion reaction)

Trauma-induced Coagulopathy (TIC) management

severe bleeding, need blood transfusion immediately

if there is >50% of blood volume lost within 3hrs (150ml per min)

bp: <90mmHg

pulse rate: >120bpm

pH level: <7.25pH

hct: <32%

hgb: 10g/dL

INR: >1.5

requirements for massive transfusion

blood pressure

pulse rate

pH level

hematocrit

hemoglobin

INR

packed RBCs

Fresh Frozen Plasma (FP-24)

Platelet concentrate - if <50,000×10^9/uL (ineffective in Immune Thrombocytopenia (ITP), Thrombotic Thrombocytopenic Purpura (TTP), Heparin-induced Thrombocytopenia (HIT))

Cryoprecipitate - fibrinogen <100mg/dL, reduce:

• Transfusion Associated Circulatory Overload (TACO)

• Transfusion Related Acute Lung Injury (TRALI)

blood components to be used in TIC management

perform TEG, PC, PT, PTT, aggregation studies

monitor entire hemostatic mechanism

monitoring TIC

plasma

key TIC management component

thawed plasma

FP-24 thawed and stored at 1-6°C, officially named as _____

may require supplementation of factor concentrates (VWF, FV, FVIII decline after 5 days ref storage)

liver disease

affects synthesis of clotting factors and specialize protein essentials

may experience bleeding due to

1. incapability to produce clotting factors

2. splenomegaly (spleen compensation) = increased sequestration of platelets

3. disrupted metabolism of vitamin K (activate factors II, VII, IX, X, and protein C, S, Z)

4. unwanted activation of coagulation mechanism related to DIC

vitamin K therapy

blood transfusion (FFP)

treatment for liver disease

liver disease - low FV

vit. K deficiency - low FVII

differentiate liver disease to Vitamin K deficiency

procoagulant deficiency

hepatitis, cirrhosis, obstructive jaundice, cancer, poisoning, and congenital disorders of bilirubin metabolism = suppress biosynthetic function of hepatocytes

alter vit k dependent factors (factors II, VII, IX, X)

dysfibrinogenemia, factor I = <100mg/dL

vWF, VIII, XIII

- commonly in the tissues

factors unaffected by procoagulant deficiency

platelet abnormalities

moderate thrombocytopenia

result from sequestration and shortened platelet survival associated with portal hypertension and resultant hepatosplenomegaly

aggregation and secretion properties are often suppressed

disseminated intravascular coagulopathy (DIC)

complication of liver disease caused by decreased liver production of regulatory antithrombin, protein C, or protein S = cannot clear activated coagulation factors

PT, PTT, TT = prolonged

D-dimer = significantly increased

acute uncompensated DIC results in

PT, PTT, TT, and D-dimer

Fibrinogen Assay

Interpretation:

>400mg/dL (elevated) in early, mild liver disease

>200mg/dL in moderate to severe liver disease

causes dysfibrinogenemia and hypofibrinogenemia

Thrombin Time Assay

Interpretation:

prolonged in dysfibrinogenemia

elevated fibrin degradation products and unfractionated heparin therapy

reptilase time assay

Interpretation:

prolonged in hypofibrinogenemia

significantly prolonged in dysfibrinogenemia

unaffected by heparin

rarely used

prothrombin time assay

interpretation:

prolonged even in mild liver disease because of des-carboxyl factors and replacing normal factors II, VII and X

partial thromboplastin time

interpretation:

mildly prolonged in severe liver disease because of DIC or des-carboxyl factors II, IX, X

Factor V

reduced in liver disease but is unaffected by vitamin K deficiency

helps distinguish liver disease from vitamin K deficiency

mild thrombocytopenia, plt = <150,000

platelet count in liver disease

mild suppression of platelet aggregation and secretion in response to most agonists

platelet aggregometry in liver disease

>2440 ng/ml or >500ng/ml fibrinogen equivalent units

quantitative d-dimer in liver disease

chronic renal failure

associated with

• platelet dysfunction (suppression of adhesion and aggregation due to GSA/phenolic compounds)

• mild to moderate mucocutaneous bleeding

renal dialysis and DDAVP

treatment for chronic renal failure

PT, PTT = normal; platelet problems

proteinuria present (kidneys unable to filter properly)

lab results in chronic renal failure (PT/PTT)?

proteinuria?

DIC

Hemolytic Uremic Syndrome

Thrombotic Thrombocytopenic Purpura

hemostasis activation syndrome that deposits fibrin in the renal microvasculature reduce glomerular function

give 3 examples of hemostasis activation syndromes

nephrotic syndrome

increased glomerular permeability

associated with chronic glomerulonephritis, diabetic glomerulosclerosis, systemic lupus erythematosus, amyloidosis, renal vein thrombosis

FII, FVII, FX, FXII, antithrombin, protein C

low-molecular weight proteins

coagulation factors and protein detected in urine during nephrotic syndrome

Vitamin K deficiency

biliary duct obstruction, fat malabsorption, chronic diarrhea may cause this

because of fat solubility and requires bile salt for absorption

vitamin k

essential for gamma carboxylation of clotting factor II, VII, IX, X

hemorrhagic disease of the newborn

because of breast milk = slows down normal flora in GIT, slows metabolism of vitamin K

sterile intestines and minimal concentration of vitamin K (vit k deficient)

coumadin

interrupts g-carboxylation of coagulation factors

liver release dysfunctional des-g-carboxyl factors II, VII, IX, X

proteins induced by vitamin K antagonists (PIVKA) factors

inactive forms of factors II, VII, IX, X, and proteins C, S, Z

prolonged PT, with or without prolonged PTT

clinical suspicion of vitamin K deficiency

oral or intravenous vitamin K

prothrombin complex concentrate (PCC)

treatment for vitamin k antagonist

auto anti-factor VIII ]

most common autoanti factor

diagnostic of acquired hemophilia (older than 60y/o, have no apparent underlying disease)

associated with rheumatoid arthritis, inflammatory bowel disease, SLE, or lymphoproliferative disease