Patho: Platelet disorders, ALTERATIONS IN THE HEMATOLOGIC SYSTEM

Blood compostition

• “Liquid Tissue” (about 5 – 6 L) 

• Composition: 

  • Red blood cells (RBCs) 

  • White blood cells (WBCs) 

  • Platelets 

  • Plasma 

What…

A. Begins with the stem cell 

B. Bone marrow stem cells proliferate and differentiate into mature blood components 

C. Colony stimulating factors (CSF) promote the growth of hematopoietic cell colonies 

D. Blood cells do not divide- they must proliferate in the bone marrow

hematopoiesis

Disorders of hemostasis:

• Mechanisms of Hemostasis (hemo- blood, stasis- stop)  

  • Vessel Spasm / Vasoconstriction 

    • Endothelial injury causes blood vessel to contract, reducing blood flow from the injured vessel.

  
  

  • Formation of the Platelet Plug 

    • Von Willebrand Factor (VWF), a blood clotting factor, is released from the endothelium- results in platelet aggregation(come together) at the site of vessel injury.  

    
    

  • Blood Coagulation(clotting) 

    • “Clotting cascade” 

    • Protects the individual from excessive blood loss.  

    • Complex process- activation of various factors in the blood 

    • Two coagulation pathways: 

      • Intrinsic pathway- begins in the circulation; initiated by circulating factor XII. 

      • Extrinsic pathway- activated by tissue factor exposed when tissues are injured. 

      • Both pathways lead to... 

        • Activation of factor X(ten), a blood clotting factor  

        • Conversion of prothrombin to thrombin 

        • Conversion of fibrinogen to insoluble fibrin threads 

        • Fibrin creates a mesh-like bed or “net” around the platelets, blood cells, and plasma, and forms a clot 

        
        

      • Many substances are necessary for the synthesis of clotting factors: 

        • Vitamin K(a fat soluble vitamin)- prothrombin, Factors VII, IX, X, and protein C 

        • Calcium- Factor IV 

        • Most clotting factors are synthesized in the liver (except VIII, XI, and XII), so if a patient with severe liver disease is not able to clot blood  

        
        

      • Blood clotting is regulated by natural anticoagulants in the body that reverse clotting effects (natural tissue plasminogen activator – tPA) 

• What happens if this process is disrupted or not working properly?  

  • Not going to be able to clot and going to have bleeding  

  
  

  • Clot Retraction 

    • Begins within a few minutes after the clot is formed 

    • Actin and myosin in the clot begin to contract 

    • Plasma (without fibrinogen) is squeezed from the clot causing it to shrink 

    
    

  • Clot Dissolution / Lysis(break down) 

    • Begins shortly after clot is formed. 

    • Activation of plasminogen 

    • Slow release of tissue plasminogen (t-PA)(a substance that dissolves clots) from injured tissues and the endothelium converts plasminogen to plasmin. 

    • Plasmin digests the fibrin strands, dissolving the clot.

Mechanisms of hemostasis (hemo- blood, stasis- stop)  

• Vessel spasm- endothelial injury

• formation of the platelet plug

• blood coagulation

• clot retraction

• clost dissolution/lysis

Mechanisms of Hemostasis:

Stage 1: Vessel spasm/vasoconstriction

Endothelial injury causes blood vessel to contract, reducing blood flow from the injured vessel. 

What injury causes blood vessel to contract, reducing blood flow from the injured vessel

endothelial injury

Mechanisms of Hemostasis:

Stage 2: Formation of the Platelet Plug 

Von Willebrand Factor (VWF), a blood clotting factor, is released from the endothelium- results in platelet aggregation(come together) at the site of vessel injury.  

 

Mechanisms of Hemostasis:

Stage 3: Blood Coagulation(clotting

• “Clotting cascade” 

• Protects the individual from excessive blood loss.  

• Complex process- activation of various factors in the blood 

• Two coagulation pathways: 

  • Intrinsic pathway- begins in the circulation; initiated by circulating factor XII. 

  • Extrinsic pathway- activated by tissue factor exposed when tissues are injured. 

  • Both pathways lead to... 

    • Activation of factor X(ten), a blood clotting factor  

    • Conversion of prothrombin to thrombin 

    • Conversion of fibrinogen to insoluble fibrin threads 

    • Fibrin creates a mesh-like bed or “net” around the platelets, blood cells, and plasma, and forms a clot 

• Many substances are necessary for the synthesis of clotting factors: 

  • Vitamin K(a fat soluble vitamin)- prothrombin, Factors VII, IX, X, and protein C 

  • Calcium- Factor IV 

  • Most clotting factors are synthesized in the liver (except VIII, XI, and XII), so if a patient with severe liver disease is not able to clot blood  

• Blood clotting is regulated by natural anticoagulants in the body that reverse clotting effects (natural tissue plasminogen activator – tPA) 

What begins in the circulation; initiated by circulating factor XII. 

intrinsic pathway

What is activated by tissue factor exposed when tissues are injured. 

extrinsic pathway

What substances are needed for synthesis of clotting factors?

• Vitamin K(a fat soluble vitamin)- prothrombin, Factors VII, IX, X, and protein C 

• Calcium- Factor IV 

• Most clotting factors are synthesized in the liver (except VIII, XI, and XII), so if a patient with severe liver disease is not able to clot blood  

Vitamin K(a fat soluble vitamin)

• prothrombin, Factors VII, IX, X, and protein C 

Calcium is what clotting factor?

Factor IV

Most clotting factors are synthesized where?

the liver (except VIII, XI, and XII),

• so if a patient with severe liver disease is not going to be able to clot blood  

What is clot retraction

1. Begins within a few minutes after the clot is formed 

2. Actin and myosin in the clot begin to contract 

3. Plasma (without fibrinogen) is squeezed from the clot causing it to shrink 

What is…..

Clot Dissolution / Lysis(break down)  

1. Begins shortly after clot is formed. 

2. Activation of plasminogen 

3. Slow release of tissue plasminogen (t-PA)(a substance that dissolves clots) from injured tissues and the endothelium converts plasminogen to plasmin. 

4. Plasmin digests the fibrin strands, dissolving the clot. 

What is the normal platelet count?

150,000-400,00 uL

Too many platelets (or increased platelet activity) = Increased risk of

too much clotting

Too few platelets = Increased risk of

bleeding

Platelet excess

• hypercoagulability States 

  • Due to... 

    • Increased platelet function  

    • Increased clotting activity  

    • Accelerated activity of clotting cascade 

• Thrombocytosis: _____>1,000,000 uL________ 

• ____Thrombus______- stationary clot formed withing the vessel  

• ___Embolus _____- traveling clot through circulatory system  

  • Blood clots narrow or completely occlude blood vessels 

• Critical Thinking Questions: 

  • How will a clot in an artery affect blood flow and oxygen delivery to cells / tissues? 

  • Arteries carry oxygenated blood,  

    • Ex: if its in your leg its carrying oxygenated blood to your foot, so this clot is going to cause ischemia or infarction 

    • Ex: if you had a blood clot in an artery supplying blood to your heart, it could cause a heart attack (myocardial infarction) 

 

• How will a clot in the venous system affect venous return to the heart? 

  • Veins carry unoxygenated blood back to the heart, 

    • Ex: if you have a blood clot in a vein in your leg, it would affect blood flow to your heart, so you would have poor venous return  

• Disorders increasing the risk of hypercoagulability: 

  • Atherosclerosis, build up of plaque in the arteries  

  • Heart failure, cause damage to endothelium, which is the initiating factor for the clotting cascade, so were going to start to develop blood clots  

  • Diabetes Mellitus, cause damage to endothelium, which is the initiating factor for the clotting cascade, so were going to start to develop blood clots 

  • Elevated platelet count, too many platelets= too much clotting 

  • Immobility, increased risk of clot formation 

  • Increased cholesterol / lipid levels, can lead to atherosclerosis  

  • Malignancies, for ex cancer can put us at risk  

  • Oral Contraceptives / Hormone replacement therapy(specifically estrogen), come with increased risk for clots  

  • Post-surgery, being cut into damages the endothelium, so that’s going to cause some clots to form  

  • Pregnancy, especially delivery causes lots of bleeding and endothelial damage  

  • Smoking

  • Stasis of blood, so anything that’s going to cause the blood to sit still, for ex immobility, causes blood to coagulate and form a clot  

Platelet excess: Hypercoagulability states?

• Due to... 

  • Increased platelet function  

  • Increased clotting activity  

  • Accelerated activity of clotting cascade 

• Thrombocytosis: >1,000,000 uL 

What is the count for thrombocytosis?

>1,000,000 uL

What is a stationary clot formed withing the vessel  

thrombus

What is a traveling clot through circulatory system 

embolus

How will a clot in an artery affect blood flow and oxygen delivery to cells / tissues? 

1. Arteries carry oxygenated blood,  

   1. Ex: if its in your leg its carrying oxygenated blood to your foot, so this clot is going to cause ischemia or infarction 

   2. Ex: if you had a blood clot in an artery supplying blood to your heart, it could cause a heart attack (myocardial infarction) 

How will a clot in the venous system affect venous return to the heart? 

1. Veins carry unoxygenated blood back to the heart, 

   1. Ex: if you have a blood clot in a vein in your leg, it would affect blood flow to your heart, so you would have poor venous return  

 

 

Disorders increasing the risk of hypercoagulability: 

• Atherosclerosis, build up of plaque in the arteries  

• Heart failure, cause damage to endothelium, which is the initiating factor for the clotting cascade, so were going to start to develop blood clots  

• Diabetes Mellitus, cause damage to endothelium, which is the initiating factor for the clotting cascade, so were going to start to develop blood clots 

• Elevated platelet count, too many platelets= too much clotting 

• Immobility, increased risk of clot formation 

• Increased cholesterol / lipid levels, can lead to atherosclerosis  

• Malignancies, for ex cancer can put us at risk  

• Oral Contraceptives / Hormone replacement therapy(specifically estrogen), come with increased risk for clots  

• Post-surgery, being cut into damages the endothelium, so that’s going to cause some clots to form  

• Pregnancy, especially delivery causes lots of bleeding and endothelial damage 

• Smoking 

• Stasis of blood, so anything that’s going to cause the blood to sit still, for ex immobility, causes blood to coagulate and form a clot  

Bleeding Associated with Platelet Deficits, causes

• Decreased platelet production 

  • Platelets are produced Bone marrow 

• Increased platelet destruction 

• Impaired platelet function 

• Platelet sequestration) in the spleen 

  • Platelet gathering in the spleen, about 30-40% of your platelets hang out in the spleen for a while, and if theyre hanging out here, they cant really make clots in the rest of the body   

Bleeding Associated with Platelet Deficits, PRIMARY MANEFESTATION?

• BLEEDING

  • Hemorrhage 

    • Overt and covert signs of bleeding 

  
  

  • Ecchymosis(bruising)  

  
  

  • Petechiae(pinpoint hemmorrhages),

    • a way to remember what this is by looking at the dot above the i in the word petechiae and image it as a petechiae  

  
  

  • Purpura, bigger than petechiae, and looks like a rash 

  
  

  • Look in body orifices, ex: mouth 

What is echhymosis

Bruising

What is petechiae?

pinpoint hemmorrhages

A way to remember what petichiae is :

by looking at the dot above the i in the word petechiae and image it as a petechiae  

What is purpura?

bigger than petechiae, and looks like a rash, large areas of brusing

What is..

• Decrease in platelet count less < 100,000 µL 

• The lower the platelets, the greater the risk of bleeding 

thrombocytopenia 

Drug-Induced Thrombocytopenia 

Adverse effect of new medication `

Heparin-Induced Thrombocytopenia 

Developed after heparin administration 

Immune Thrombocytopenic Purpura 

Platelet antibodies = destruction of platelets 

 

Thrombotic Thrombocytopenic Purpura 

Combination of thrombocytopenia, hemolytic anemia, renal failure, fever, and neurologic abnormalities 

Bleeding Associated with Coagulation Deficiencies 

• Inherited Disorders 

  • Von Willebrand Disease 

    • Autosomal dominant disorder 

    • Usually diagnosed in adults 

    • So for ex if a person with this disorder gets a cut they are going to bleed for a long time, much longer than someone without this disease 

  • Hemophilia A 

    • X linked recessive disorder (see it more often in males than females) 

    • Mostly males, mostly children 

    • Deficiency in Factor VIII(clotting factor) 

    • May experience bleeding into joints 

• Acquired Disorders 

  • Liver Disease- the liver is responsible for synthesizing all except three coagulation factors. 

  • Vitamin K Deficiency- Vitamin K is synthesized by intestinal bacteria and is essential for the activation of several coagulation factors. 

What is Von Willebrand disease?

1. Autosomal dominant disorder 

2. Usually diagnosed in adults 

3. So for ex if a person with this disorder gets a cut they are going to bleed for a long time, much longer than someone without this disease 

What is Hemophilia A

1. X linked recessive disorder (see it more often in males than females) 

2. Mostly males, mostly children 

3. Deficiency in Factor VIII(clotting factor) 

4. May experience bleeding into ___joints____ 

Bleeding Associated with Coagulation Deficiencies:

Aquired disorder: LIVER DISEASE

the liver is responsible for synthesizing all except three coagulation factors. 

Bleeding Associated with Coagulation Deficiencies:

Aquired disorder: VITAMIN K DEFICIENCY

Vitamin K is synthesized by intestinal bacteria and is essential for the activation of several coagulation factors. 

What is Disseminated Intravascular Coagulation (DIC) ?

• Summary: widespread bleeding and clotting at the same time!!

• Pathogenesis

  • Endothelial damage —> activation of the clotting cascade 

  • Widespread clotting with multiple thrombi and emboli in vessels all throughout the body (tissue perfusion is impaired) 

  • Platelets and clotting factors are depleted faster than replaced 

  • Widespread clotting stimulates fibrinolysis, contributing to bleeding 

  • The ability to form clots is depleted —> hemorrhage eventually occurs 

• Precipitating factors:

  • Cancer 

  • Infection 

  • Obstetric complications 

  • Shock 

  • Trauma 

  • Vessel damage 

• life-threatening problem

Pathogenesis of Disseminated Intravascular Coagulation (DIC)

1. Endothelial damage —> activation of the clotting cascade 

2. Widespread clotting with multiple thrombi and emboli in vessels all throughout the body (tissue perfusion is impaired) 

3. Platelets and clotting factors are depleted faster than replaced 

4. Widespread clotting stimulates fibrinolysis, contributing to bleeding 

5. The ability to form clots is depleted —→ hemorrhage eventually occurs 

Precipitating factors of Disseminated Intravascular Coagulation (DIC) 

• Cancer 

• Infection 

• Obstetric complications 

• Shock 

• Trauma 

• Vessel damage