Bleeding and Clotting Disorders

Defects in primary hemostasis

Easy bruising, petechiae, purpura, ecchymoses, and spontaneous

bleeding, especially from mucosal surfaces

petechiae

small dots

purpura

bleeding into the skin

ecchymoses

large superficial hemorrhaging

Defects in secondary hemostasis

hemarthrosis

or muscles or hematomas: With these disorders can

see spontaneous bleeding severe factor deficiency

or mild factor deficiency

hemarthrosis

Prolonged deep bleeding into joints

severe factor deficiency

spontaneous bleeding 

post-injury

mild factor deficiency

Combination defects

Multiple site bleeding occurs in severe combined defects (DIC). Platelet activity and coag proteins are related so disorders of one can affect the other since platelets provide phospholipid binding sites for clotting factor interaction.

Thrombocytopenia

spontaneous skin and mucosal

membrane bleeding, resulting in petechiae.

Coag disorders

tend to bleed after a traumatic incident,

but not right away

Platelet disorders

tend to bleed from skin and mucous

membranes with no apparent preceding trauma

Factor deficiencies

tend to bleed into joints and soft

tissue

Clot removal is accomplished by which system

a) fibrinolysis

b) hemostasis

c) anticoagulation

d) thrombosis

fibrinolysis

For the control of bleeding all of the following characteristics are true except:

a) PF3 is important in activation of some coagulation factors

b) platelet adhesion is essential

c) VIII:vWF acts as a glue for platelet-collagen binding to occur

d) it is not necessary for platelets to aggregate with one another

it is not necessary for platelets to aggregate with one another

A disorder associated with platelet dysfunction despite a normal platelet count is:

von Willebrand disease

protective mechanisms against thrombosis include all of the following except:

a) normal blood flow

b) natural in vivo anticoagulants (such as AT-III)

c) cellular regulators that block the activation or action of plasmin

d) antibodies produced by lymphocytes to block thrombin

d) antibodies produced by lymphocytes to block thrombin

Evaluation of Potential

Bleeding Disorder

HISTORY, symptoms, age, Type and sites of bleeding, Spontaneous/ result of trauma, Platelet count, PT, PTT, PFA

Hereditary Bleeding Disorders

von Willebrand Disease (disorder of plts and coag), Hemophilia A (coagulation), Hemophilia B (coagulation), Other factor deficiencies (coagulation), Hereditary Platelet Disorders (platelets)

Acquired Bleeding Disorders

DIC (plts and coag), ITP (low plts), TTP and HUS (low plts), Bleeding caused by deficiency of vitamin K dependent factors

(coagulation), Bleeding associated with liver failure (plts and coag)

Are heriditary bleeding disorders more common than acquired bleeding disorders?

No, they are all less common except for vWD

Von Willebrand Disease problem

Most common hereditary bleeding disorder, Autosomal dominant, Either there is not enough of von willebrand factor or it doesn’t function properly

what does von willebrand factor do?

it glues the platelets to the subendothelium and is

the carrier molecule for Factor VIII

Von Willebrand Disease severity of bleeding

varies: can be extremely heavy menses,

excessive nosebleeds, blood loss from tiny cuts, easy bruising

Treatment for Von Willebrand Disease?

drug called desmopressin which stimulates patients

endothelial cells to release vWF, cryoprecipitate (creamy white

bag of plasma proteins from a single human donor and/or Factor

VIII concentrate

Hemophilia A

most common coagulation factor deficiency where Factor VIII is decreased or totally absent, X-linked recessive inheritance

Hemophilia A severity

depends on how much Factor VIII the patient can make, Type of bleeding is recurrent, painful bleeding into joints following

trauma, prolonged bleeding after dental extractions, spontaneous

mucosal hemorrhage.

Hemophilia A Treatment

desmopressin to stimulate release of Factor VIII (along with

vWF), small amounts of Factor VIII replacement to prevent patient making

antibodies against it

Hemophilia B

Much less common that Hemophilia, A Little to no Factor IX, X-linked recessive inheritance

Hemophilia B severity

depends on how much Factor IX the

patient can make, Type of bleeding is recurrent, painful bleeding into joints

following trauma, prolonged bleeding after dental

extractions, spontaneous mucosal hemorrhage.

How to distinguish between

Hemophilia A and Hemophilia B?

Need to do Factor Assays

Hemophilia B Treatment

Recombinant Factor IX concentrate

Factor XI deficiency

seen mainly in Ashkenazi Jews and

usually causes excess bleeding only after trauma such as

surgery

Factor XIII deficiency

causes a severe bleeding tendency,

usually presenting with umbilical stump bleeding

PT/INR

To evaluate the extrinsic and common

coagulation pathways; monitor Coumadin

therapy

PTT

To evaluate the intrinsic and common

coagulation

pathways; monitor heparin therapy

TT- thrombin time

To look for a fibrinogen problem; to monitor

heparin therapy

FDP/D-dimer

To look for fibrin split products which will help

rule out a clot

Fibrinogen

To monitor fibrinogen levels during a massive

transfusion

Platelet Function

To evaluate primary hemostasis (used to be

BT)

Mixing Studies

Performed after abnormal PT/PTT to

determine if the patient has a factor

Bernard-Soulier Syndrome

Autosomal recessive, Abnormality of glycoprotein Ib, which binds

vWF, so their plts can’t bind to the subendothelium, severe bleeding

Glanzmann Thrombasthenia

Autosomal recessive, Abnormality of glycoprotein IIb-IIIa, so their

plts don’t aggregate, Severe bleeding

Gray Platelet Syndrome

Plts have few or no alpha granules- look gray, giant

plts, mild bleeding

DIC- Disseminated Intravascular Coagulation

Thrombo-hemorrhagic disorder that occurs as a complication to many other conditions, coagulation system is triggered, resulting in

many small fibrin clots (which trap platelets)

throughout the body, These small clots destroy RBC’s, causing a hemolytic

anemia and block

small vessels, All of this clotting uses up the platelets and clotting

factors, causing bleeding, Then, the body breaks down fibrin into FDP, which in

turn inhibits clotting and aggravates the bleeding

problem

what makes a person go into DIC?

anything that will release procoagulant

substances into the blood: Complications during pregnancy or delivery, Adenocarcinoma, Venomous snake bites, AML- M3, Things that damage endothelium or tissue: Toxin-producing bacterial infections, Trauma or burns, Vasculitis

DIC Signs of bleeding and clotting:

Bleeding from venipuncture site or surgical wounds, GI, lung, or obstetrical bleeding, Petechiae, Gangrene, Symptoms are often in multiple organ systems such as

respiratory, nervous, renal, and vascular

DIC Treatment

find out the underlying cause then, supportive treatment: fresh frozen plasma (has

coag factors), cryoprecipitate (has fibrinogen), PLTS, RBCS

ITP- Idiopathic Thrombocytopenic Purpura

A disorder in which the patient makes antibodies against their platelets; has acute and chronic forms

Chronic ITP

most common in women under age 40,

slow onset, can be seen with lupus, HIV, CLL.

Acute ITP

most common in children, abrupt onset

usually following a viral illness, self-limiting

ITP lab tests

Low PLT count, large plts on smear, Coag tests are normal

ITP Treatment:

glucocorticoids (inhibit phagocytic function)

ITP relapse

splenectomy

TTP- thrombotic thrombocytopenic purpura

platelets become activated, clump, form clots that get stuck in small vessels, leading to organ dysfunction, blood in urine, jaundice, bleeding, bruising, fever

TTP treatment

plasmapheresis to get rid of the

antibodies, steroids

HUS-hemolytic

same as TTP but

associated with gastroenteritis children and the elderly are at risk, contaminated food causes it usually, bloody

diarrhea followed by renal failure

DIC PT/INR and PTT

problem is activation of coagulation,

so the PT/INR and PTT are both prolonged

thrombotic microangiopathies PT/INR and PTT

the problem is platelet clumping, so the PT/INR and PTT are normal

Deficiency or abnormality of vitamin K dependent factors cause

Coumadin (qualitative abnormality of the

factors, not quantitative), poor diet

T or F: Most patients who develop thrombi do NOT have a thrombotic disorder.

True

THROMBI types

“White clot”, “Red clot”

“White clot”

involving mostly platelets, found in arteries, causes MI, strokes, Associated with hypertension, hyperviscosity, qualitative

platelet abnormalities, atherosclerosis

“Red clot”

involving RBC’s and fibrin, found in veins, causes DVT and PE, Associated with endothelial damage, slow blood flow,

hypercoagulability

Atherosclerosis

plaque build up in the endothelium,

narrowing the blood vessels

CAUSES OF EMBOLI

Endothelial damage, Abnormal blood flow, Hypercoagulability

Stasis-

varicose veins, atrial fibrillation (blood collects in the heart

because it’s not being pumped uniformly)

Turbulence-

occurs with congenital heart defects (cardiac valve

stenosis)

Hereditary thrombotic disorders

Factor V Leiden, Antithrombin III deficiency, Protein C deficiency, Protein S deficiency, Factor II (prothrombin) gene mutation, Hyperhomocysteinemia

Acquired thrombotic disorders

Antiphospholipid antibody syndrome

Factor V Leiden

Single point mutation of the Factor V gene, Treatment is Coumadin and avoiding all of the associated risk

factors

Antithrombin III deficiency

all three coagulation pathways are affected, 

Protein C deficiency

Factors V and VIII are not inactivated so clotting cant be shut down

Protein S deficiency

Factors V and VIII are not inactivated so clotting cant be shut down

Factor II (prothrombin) gene

Gene mutation that causes the production of excess prothrombin

Hyperhomocysteinemia

elevated levels of Homocysteine, associated with thromboses and atherosclerosis

Antiphospholipid antibody syndrome

Patients produce antibodies to various phospholipids, causing thrombosis,

fetal loss, renal failure

Anticoagulant therapy is needed following several clinical situations

such as:

an episode of thrombosis, after some surgeries, in heart valve and chamber disorders where there is an increased

risk of clotting.

Antithrombin (anti-thrombolytics) agents

Antiplatelet drugs, Anticoagulant drugs, Thrombolytic drugs

Antiplatelet drugs

Inhibit platelet activation and aggregation, effective in treating arterial disease

Anticoagulant drugs

Inhibit thrombin and fibrin, Used to treat venous thrombosis

Thrombolytic drugs

Used to breakdown fibrin clot

Antiplatelet drug examples

Aspirin (peak for 1 hour), heparin (short term), coumadin (long term)

What is the anticoagulant of choice for routine coagulation assays?

Sodium Citrate

The prothrombin assay requires that the patient’s citrated plasma be combined with

Calcium chloride and thromboplastin

What does the silicate (kaolin) do in the test system for APTT?

activates tissue thromboplastin

which factor is measured by the prothrombin assay?

II, X

What is the most accurate POCT coagulation assay used to monitor heparin?

Activated partial thromboplastin time

Which statement accurately describes a thrombosis that is arterial?

A. It is considered a “white clot”

• B.

It can cause heart disease, heart attacks, and strokes

• C. It involves mostly platelets

• D. It is associated with hypertension, hyperviscosity, and

atherosclerosis

• E. All of these accurately describe an arterial thrombosis

• F. These statements accurately describe a venous thrombosis

E. All of these accurately describe an arterial thrombosis

Which of the following should be avoided if you are at risk

for thrombosis?

• A. Smoking

• B. Oral contraceptive use

• C. Frequent airline travel on particularly long flights

• D. Alcohol consumption

all should be avoided but especially smoking

Which of the following statements about anticoagulant therapy is

FALSE?

• A. Heparin is given through IV and inactivates thrombin

• B. Heparin dosage is monitored by PT/INR.

• C. The long term solution for patients on anticoagulant therapy

is oral anticoagulants.

• D. Warfarin is an oral anticoagulant and acts as a Vitamin K

antagonist.

• B. Heparin dosage is monitored by PT/INR.