Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Hematosis - 2024 > Week 9 > Flashcards

Week 9 Flashcards

1
Q

What is the clinical presentation of bleeding
Site
Onset
Presentation

A

Site
Localized - one site (trauma or acute injury)
Generalized- more than one site (defect in primary or secondary hemostatsis)

Onset
Right after trauma
delayed or recurring
spontaneous

Presentation
Mucocutaneous - skin and mucous membranes
Anatomic - deeper tissue involvement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

When you look at patient history what is looked at

A

Account of bleeding episode
-onset, location, pattern, duration and severity

history of bleeding
-after surgery, pregnancy, diabetes, transfusions, anemia

family history
age and gender
diet and medication history

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Generalized Mucocutaneous presentation:
petechiae
purpura
ecchymosis - bruising

A

-if there is more then one unprovoked hemorrhagic lesion it indicates primary hemostasis disorder
-associated with :
vascular disorders
thrombocytopenia
qualitative platelet disorders
vWD

Petechiae - Pinpoint hemorrhages in skin 1mm dia

Purpura - Hemorrhages greater than 3mm in diameter, caused by extravasated (seeping) red blood cells

Ecchymosis (Bruising) - Hemorrhages greater than 1cm with irregular shapes, seen after trauma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Anatomic (soft tissue) presentation:

A

-acquired or congential defects in secondary hemostatis
-uncontrolled fibrinolysis, presence of factor inhibitors, factor deficiencies
-recurrent or excessive bleeding after minor trauma
-bleeding can be spontaneous
-bleeding mostly internal joints (hemathroses), body cavities, muscles, CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what can defects in 2ndary hemostasis result from

A

Decreased or abnormal synthesis of factors
-Acquired coagulopathy - Disease state
-Congenital coagulopathy - Loss or mutation of gene

Loss or consumption of factors
-Acquired - Initiation of coagulation

Production of abnormal interfering substances
-Inhibitors (antibodies) that interfere with coagulation pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are some indications for congenital disorders

A

-family history of bleeding
-excessive bleeding from umbilical cord
-repeated hemorrhages in childhood/adulthood
-chronic petechaiae, purpura
-bleeding into joints, CNS or soft tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Congenital Deficiencies how are they caused and where are they seen

A

-single factor deficiency - spontaneous or inherited gene mutation coding for factor
-can be multiple factor deficiencies or platelet def
-can be in all pathways
-common are vwd, hemo A (fviii def) and Hem B (FIX def), PLT disorders

-in rare instances
-inherited fib, prothom,
severe factor def - uncommon and found in young children

mild congenital deficiencies - asymp, until pt reaches adulthood or has physical challenges like dental procedure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Von Willebrand Disease (VWD)

A

VWF & FVIII
-most prevalent congenital mucocutaneous bleeding disorder
-autosomal dominant or recessive inheritance -equally in men and women
-caused VWF germline mutations producing quantitative VWF (Type 1 and 3 VWD) or qualitative VWF - type 2 VWD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is VWF

A

-plasma procoagulant and acute phase reactant
-LARGE multimeric glycoprotein
-circulates in low concentrations in plasma
-produced by megakaryocytes and ECs
-stored in alpha granules of PLTs and endothelial cells Weibel-Palade bodies
-released due to BV injury
-can fluctuate given a persons blood type, inflammation, hormones, physical stress
-increased in 2nd and 3rd trimester of pregnancy due to increase in estrogen. The decrease after delivery causes acute post partum hemorrhage

-monomer with 4 binding sites:
Platelet glycoprotein Ib/IX/V receptor
Platelet glycoprotein IIb/IIIa receptor
Collagen binding site
Factor VIII binding site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What role does VWF play in hemostasis

A

-binds exposed subendothelial collagen during trauma of vasculature
-platelets attach to vwf with GPIb/IX/V receptor
-VWF:GPIb/IX/V activates platelets to express a second VWF binding site, GPIIb/IIIa
-GPIIb/IIIa binds VWF and fibrinogen to mediate irreversible platelet-to-platelet aggregation
-VWF carrier protein of FVIII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the function of VWF

A

-initiate primary hemostatis by bridging PLTs and subendothelial collagen
-supports PLT aggregation with receptor site
-transports FVIII in blood increasing half life by protecting it from proteolysis in plasma.
-carrier molecule role in 2ndary hemostasis
-regulated by ADAM13- enzyme that prevents unnecessary clotting
-abnormalities lead to severe bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

When doing VWF testing why do a cbc and pt/aptt

A

CBC
-rule out thrombocytopenia as cause of bleeding
-can be normal or decreased because of subtype

PT and APTT
-to rule out coag factor deficiencies other than VWF def
-APTT can be normal or prolonged depending of FVIII plasma concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Subtype Classifications are determined in lab for VWF testing

A

Plasma concentration
-VWF:AG ratio QUANTITATIVE immunoassay

VWF activity by RCOF assay
-QUALITATIVE look at VWF function with VWF:RCo assay

FVIII activity assay (FVIII:C)
-when FVIII are less than 30% of normal then anatomic soft tissue bleeding accompanies the mucocutaneous bleeding pattern of VWD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Von Willebrand Disease
(VWD)
Pathophysiology

A

-Quantitative VWF abnormality = reduced plasma concentration of VWF and FVIII
-Qualitative VWF abnormality = VWF function reduced (affecting PLT adhesion and aggregation)
-pts with decreased plt adhesion or mucosal/mucocutaneous bleeding -epitaxis, ecchymosis is impaired primary hemostasis
-Quantitaive VWF def can also create FVIII deficiency that can lead to impaired secondary hemostasis with possible anatomic bleeding

there are 3 types
Type 2 has 2A, 2B, 2M, 2N -autosomal hemophilia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the Ristocetin Cofactor Assay

A

VWF:RCo (qualitative) analysis

-platelet aggregation test with pt PPP with reagent platelets and ristocetin

-PLT aggregation due to Ristocetin only happens in VWF presence
-if Ristocetin is added to pt plasma that doesnt have VWF then the reagent PLT will not clump

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how to interpret VWD Laboratory Testing

A

-look at the ratio of activity to AG concentration
VWF:RCo : VWF:Ag

-errors in quantification vs errors in VWF function

-Qualitative VWD is suggested when ratio of Ristocetin assay to the antigen concentration is <0.5 = Type 2 VWD

Subtypes are determined by
VWF Multimer Size patterns (P.A.G.E)
Polyacrylamide Gel Electrophoresis - separated by size not charge
-qualitative assay that looks at overall size distribution of VWF multimers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is hemophilia A

A

-CLASSIC hemophilia
-single factor def and congenital
-FVIII deficiency slows coag pathway production of thrombin leading to bleeding
-FVIII protein translated from X chromosome. Deletions, stop codons and missense mutation cause the QAUNTITATIVE def in FVIII
-marked by anatomic soft tissue bleeding
APTT ALWAYS PROLONGED
-Normal plt aggregation

manifests as
-deep muscle hemorrhages
-hematomas
-wound oozing
-bleeding into CNS, peritoneum, GI tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

how are pt with HEMOPHILIA A treated

A

-DDAVP which helps to release VWF from storage to raise FVIII activity
-FVIII concentrate, “on demand” therapy
Recombinant FVIII concentrate (rFVIII) OR
Human plasma-derived FVIII (pdFVIII) - plasma donors
-CRYO - rare from plasma donors FVIII, VWF and FI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is Hemophilia B

A

-Christmas disease
-single factor def and congenital- X linked
-marked by anatomic soft tissue bleeding - almost indistinguishable from Hemo A
-FIX def that reduces thrombin production

Patients are treated with:
Recombinant FIX concentrate
Gene therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What lab tests are done with PT with HEM A and B

A

-first the testing will have similar results
PT – Normal
APTT – Prolonged
Thrombin time – Normal
Fibrinogen assay – Normal

Corrected mixing studies
Factor assays – FVIII decreased (Hemophilia A)
Factor assays – FIX decreased (Hemophilia B)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is hemophilia C

A

-Rosenthal syndrome
-FXI deficiency
-autosomal recessive
-severity of bleeding does not correlate to FXI assay

PT – Normal
APTT – Prolonged
Patients are treated with plasma infusions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What will we see in Other Congenital Single-Factor Deficiencies

A

-Rare autosomal recessive mutations associated with consanguinity

-Def in Fibrinogen, Prothrombin, FV, VII, X, or XIII. Use PT, APTT, TT to tell which factor def you have and THEN follow with factor specific assays

-causing anatomic hemorrhage

17
Q

FVII deficiency

A

Inherited
Bleeding may not reflect FVII activity level
PT prolonged, APTT normal
Target of treatment is to obtain levels of 10-30%

18
Q

FX deficiency

A

-Inherited or may be acquired – amyloidosis, paraproteinemia, or antifungal therapy
-Both PT and APTT prolonged
-Target of treatment is to obtain levels of 10-40%

19
Q

FXIII deficiency

A

-rare
-happens in 3 forms all related to FXIII structure
-PT, APTT and TT – Normal
-pt can form weak clots (non cross linked) that dissolve
REMEMBER FXIII IS ALSO FIBRIN STABILIZING FACTOR
-do reflex testing - 5M Urea testing , FXIII quantitative

20
Q

What is trauma induced coagulopathy - TIC
Acquired disorder

A

-fatal hemorrhage in trauma related deaths
-triggered by systemic shock
-leads to Coagulopathy and hemorrhage by ADAMS13 reduction, TF release, Coaf factor activation, hyperfibrinolysis and loss of coag control proteins

treatment:
Massive Transfusion (RBC Infusion) + Plasma (Thawed plasma or FP-24) + PLT concentrate (1:1:1- in equal amounts - approximating makeup of whole blood)

21
Q

Liver disease - Acquired disease

A
  • bleeding because of liver disease can be localized or generalized, mucocutaneous or anatomic

-Mucocutaneous bleeding - associated with thrombocytopenia and decreased platelet function

-Anatomic or soft tissue bleeding occurs because of procoagulant dysfunction and deficiency

-symptoms are jaundice and abdominal tenderness

22
Q

Liver Disease – Procoagulant Factor Deficiency

A

-liver produces factors and coag regulatory proteins
-if hepatocytes are damaged then factors are decreased
-VWF is an exception – VWF is produced by megakaryocytes and endothelial cells
-FVIII also an exception – is also produced by vascular endothelial cells

-Vitamin K - dep factors also affected (FII, VII, IX, and X, and control proteins C, S, and Z)
-they are released without a 2nd carboxyl group and cannot participate in coag
-FVII affected first because it has the shorted half life

23
Q

What would you see in liver disease lab results
PT, APTT, PLT , FIB

A

PT
-prolonged
-sensitive to FVII activity, it is a early marker for liver disease

APTT
-prolonged in severe disease

Plt count
-mild thrombocytopenia

Fib
-increased at first then reduced/abnormal later in disease as the disease severity increases

24
Q

Liver Disease – Factor Deficiency or Dysfunction
Factor V

A

-Non-vitamin K-dependant, labile factor
-Reduced in liver disease (as well as FVII)
-Assessed by FV assay
-Not reduced in dietary Vitamin K deficiency
-Helps to differentiate the two diseases

25
Q

Liver Disease – Factor Deficiency or Dysfunction
Fibrinogen

A

-Elevated in early liver disease - because is an APR
-Moderate or severe liver disease
-Dysfibrinogenemia occurs – fibrinogen is coated with sialic acid- leading to poor fibrinogen function and resulting in general anatomic bleeding
-Marked decrease in end-stage liver failure
-Fibrinogen levels severely decreased (hallmark)

26
Q

Liver Disease - Non-Factor Issues

Platelet Abnormalities
Systemic Fibrinolysis

A

Platelet Abnormalities
-moderate thrombocytopenia because of shortened PLT survival, low production
-seen in reduced PLT aggregometry testing
-cause would be portal hypertension and hepatosplenomegaly

Systemic Fibrinolysis
-diseased liver does not clear circulating plasmin which is a fibrinolytic serine protease

27
Q

Liver Disease – Treatment

A

Oral or IV Vitamin K therapy- short lived because liver metabolism is impaired

Transfusion of thawed Frozen Plasma, collected from normal donors - with ALL coaf factors

Cryoprecipitate in severe cases (Fibrinogen <0.5 g/L= bleeding is imminent) - VERY CONCENTRATED FIB

Liver transplant in severe cases of the disease

28
Q

What is DIC

A

-uncontrolled hemostasis activation secondary to disease process
-causes both bleeding and clotting because platelets and coagulation factors are being used up at a fast rate
-CONSUMPTIVE COAGULOPATHY
-affects primary hemo (plt decrease), and 2ndary hemostasis (factor consumption = increase in PT APTT)
-causes clot formation in small vessels
-sets up systemic toxic and inflammatory processes that decrease flow to tissues, organs
-moderate to life threatening
-Acute is fatal and DIC can be chronic

29
Q

What is a complication that can arise from liver disease

A

DIC
-low production of regulatory proteins (AT, Protein C and S)
-release of activated procoag from degenerating hepatocytes that cant be cleared by the liver

30
Q

Disseminated Intravascular Coagulation (DIC)
Lab results and PBS MORPH

A

Lab results
-Platelet count decreased
-PT, APTT and TT are all prolonged
-Fibrinogen level may be decreased
-D-Dimer positive

PBS Morphology
-Intravascular fibrin production –
Microangiopathic hemolytic anemia (MAHA) - with thrombocytopenia and schistocytes

31
Q

how do you treat DIC

A

Transfusion with :
Thawed frozen plasma: with ALL coag factors

Cryo - Concentrates FIB, FVII, VWF

Platelet or RBC transfusion
Heparin slows thrombotic process
Routine tests to monitor therapy
-PT, APTT, Fibrinogen, D-dimer, CBC (RBC Morph/PLT estimate), and Heparin assay

32
Q

What is Renal disease
acquired disorder

A

-chronic renal failure associated with PLT dysfunction causing mucocutaneous bleeding
-altered plt function is the cause of bleeding
-adhesion and aggregation suppressed because of antiplatelet effects of compounds like guanidinosuccinic acid or Phenolic compounds coating PLT (PRIMARY affected)

-Thrombocytopenia & Anemia contribute to bleeding

-PT/APTT results are normal - -2º hemostasis typically unaffected

-Treatment - Dialysis, RBC transfusions, or EPO therapy

33
Q

Vitamin K deficiency
acquired
how to solve

A

-found in food - leafy greans
-bowel flora produces Vit K
-needed daily body stores are limited

caused by :
-AB use
-malabsorption
-fad diets or IV nutrition
-hemorrhagic disease of the newborn , breastfeeding delays establishment of gut flora
-Coumadin overdose common in lab resulting in lack of function in VitK dep factors

results in
-mod to severe bleeding
-if Coumadin overdose - oral Vit K therapy 3 hours
-transfusion on frozen plasma

34
Q

Vitamin K Deficiency Lab Results
factors affected:

A

Factors affected
II, VII, IX, X (& Protein C, S, and Z)

PT
PT is prolonged much before APTT
Due to short ½ life of FVII - first to decrease

APTT
APTT is eventually prolonged (deficiency must be severe before the APTT will be prolonged)

Fibrinogen
Fibrinogen levels are normal or slightly decreased

35
Q

Autoanti-FVIII Inhibitor and Acquired Hemophilia

A

-acquired autoantibodies have been found in non hemo pt and can inhibit FII (prothrombin), V, VIII, IX, XIII, and VWF
-Autoantibodies against FVIII are most common
-autoanti-FVIII is diagnostic of acquired hemophilia, seen in pt over 60 with no underlying issues causing severe anatomic bleeding into soft tissue
-autoAB for other procoags are rare

36
Q

Acquired hemophilia is occasionally associated with:

A

Rheumatoid arthritis (RA)
Inflammatory bowel disease
Systemic lupus erythematosus (SLE)
Lymphoproliferative disease
Pregnancy (acquired hemophilia triggered 2-5 months after delivery)

37
Q

Clot-Based Assays to Detect Acquired Hemophilia

A

-if there is sudden hemorrhage that looks like acquired hemophilia - PT, APTT, and TT ordered
-If FVIII inhibitor present (most common inhibitor) -
PT and TT- normal (most likely)
APTT- prolonged
Reflex with Mixing Study and Factor/Inhibitor assay

FVIII assay - likely to show FVIII activity of 40% or less

38
Q

Acquired von Willebrand Disease

A

-mod to severe mucocutaneous bleeding
-can be suspected in ANY pt with recent bleeding with no bleeding history
-Symptoms similar to congenital VWD

Bleeding caused by either:
Decreased VWF production
Adsorption of VWF to abnormal cell surfaces OR
Specific VWF Autoantibody

Can be associated with:
Hypothyroidism
Autoimmune disorders
Lymphoproliferative and Myeloproliferative disorders
Intestinal disorders
Congenital heart disease
Pesticide exposure
Uremia

39
Q

Lab results
Acquired von Willebrand Disease

A

PT – Normal (not affected)

APTT - Prolonged (moderately)
- VWF available to support FVIII

As in congenital VWD, diagnosis based on VWF:RCo : VWF:AG ratio
-Diminished VWF activity and VWF antigen levels

40
Q

Thrombotic Disorders
Antiphospholipid Antibodies APA

A

-autoantibody immunoglobulins that bind protein-phospholipid complexes (IgM or IgG isotypes)
Includes antibodies-
Lupus anticoagulant
Anticardiolipin
Anti-β2-GPI
Anti-DNA

-Non-specific inhibitors
-manifests are unexplained venous or arterial thrombosis, thrombocytopenia or recurrent fetal loss

41
Q

Lupus Anticoagulant (LAC)
Antiphospholipid Antibody

A

-Most common APA
-found in 50% of pt with SLE (Systemic Lupus Erythematosus)
-antibodies promote abnormal clotting in vivo - THROMBOTIC
-Blocks or binds phospholipid in the PT/APTT reagent – preventing clotting in vitro (non-specific inhibitor)

42
Q

Lab Investigation of Inhibitor - LAC

A

-APTT prolonged

-Mixing studies (APTT remains prolonged or Mix not corrected)

Lupus anticoagulant profile- Dilute Russell Viper Venom Test (DRVVT)
-most specific LAC assay
-based on ability of venom of Russell viper to induce thrombosis
-coag in venom activates FX which activates prothrombin to thrombin in presence of FV and phospholipid
-LAC AB interfere with clot promoting of phospholipid in vitro causing prolonged clotting time

43
Q

Thrombotic Disorders associated with Fibrinogen Activity

A

Hypofibrinogenemia - FIB level less than 1 g/L
Afibrinogenemia - absence of fibrinogen
Dsyfibrinogenemia - presence of FIB that is biochemically abnormal and non-functional

44
Q

Heparin-Induced Thrombocytopenia (HIT

A

-Consequence of immune response to UFH and LMWH
-Results in reduced PLT count via PLT activation, inflammation, and thrombosis

45
Q

Laboratory Investigation of Bleeding

A

CBC
HGB, HCT, PLT count, and RET
-can show anemia from bleeding and BM response
-normal in inherited factor deficiencies
- abnormal in acquired disorders
-Depends on underlying cause of disorder

PT or APTT or both are prolonged

Thrombin time (qualitative analysis of FIB activity)
-If both PT & APTT are abnormal – common pathway?
-Start with Fibrinogen (FI) deficiency

Can be affected by inhibitors:
-Heparin, DTIs (sample contamination or therapy)
-Fibrinogen/fibrin degradation products
-Non-specific Inhibitors (LAC)
-Specific Factor Inhibitors/Antibodies

Fibrinogen assay (quantitative)

Platelet Function Tests - specific to confirm disease

Factor Assays - to determine what factor is deficient and % activity

46
Q

Correction/Mixing Studies

A

-performed on plasma used to distinguish factor deficiencies from factor inhibitors

Differentiate between:
Factor deficiencies (single or multiple) OR
Specific Factor Antibodies or Inhibitors OR
Non-specific Antibodies or Inhibitors

-normal PT or APTT need 50% of normal levels in circulation

-mixing studies help to determine next steps to diagnose cause of abnormal PT and APTT

47
Q

Reflex Tests for Factors

A

-When fibrinogen and an inhibitor have been ruled out, prolonged result(s) are the result of single factor OR multi-factor deficiency

-FACTOR ASSAYS determine which factor(s) are deficient
FVII and FVIII are most common

-Only PT or APTT Prolonged - specific assay

-Both PT & APTT Prolonged- factors from common pathway

48
Q

What is the 5M urea solubility test

A

-assess FXIII deficiency or inhibition
-FXIII is insoluble in urea
-without FXIII, fibrin clot will dissolve rapidly in presence of urea
-Positive results should be confirmed by FXIII assay
Quantitative FXIII activity assay

-clots PPP with CaCL2
-visual inspection for clot at 1, 2, 3, 4, and 24 hours

clot at 24hrs = Normal FXIII levels
No clot at 24hrs = Abnormal FXIII levels

a decrease in clot size, fragmentation, cloudiness which is a FXIII abnormality
-abnormal at less than 2 %

Hematosis - 2024 (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions