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MD2011 > Week 5 HRM > Flashcards

Week 5 HRM Flashcards

0
Q

What is TTP?

A

The pathophysiology of TTP reflects a deficiency of ADAMTS13, the von Willebrand factor (vWF) protease that cleaves ultra-large vWF (UL-vWF) into smaller multimers. Without this, vWF accumulates and binds more platelets.

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1
Q

What would you see in RBC morphology of TTP?

A

Broken/fragmented RBCs and no/ limited platelets

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2
Q

List the types of vWF disorders

A 
Type 1 decreased production of VWF
Type 2 a decrease in large multimers
Type 2b mutation in VWF that causes increased affinity towards platelets and increased agglutinagion
Type 3: total absence of VWF
Type 4 pseudo von wilebrands disease
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3
Q

Describe what petechiae look like?

A

Small pin sized spot on the skin. Due to bleeding into the skin

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4
Q

Describe what purpura look like?

A

Purple spots on the skin (larger than petechiae)

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5
Q

Describe what echymosis look like?

A

Larger spots on skin than purpura

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6
Q

What is a haematoma?

A

A solid swelling of clotted blood within the tissues

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7
Q

Describe superficial bleeds

A

Usually due to platelet or blood vessel disorders - show signs of petechiae and purpura

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8
Q

Describe deeper bleeds

A

Usually due to coagulation disorders (internal bleeding, haematoma, joint bleeds)

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9
Q

What are the 3 main categories of bleeding disorders?

A
  1. Blood vessel disorders
  2. Platelet disorders
  3. Coagulation disorders
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10
Q

What are the top 5 bleeding disorders to know?

A
  1. DIC
  2. Thrombocytopenia immune
  3. Vitamin K deficiency
  4. Von Willebrand Disease
  5. Haemophilia A & B
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11
Q

What is DIC? (brief summary of what it is)

A

Disseminated intravascular coagulation. Characterised by a massive systemic activation of the blood coagulation system. Results in the deposition of fibrin , leading to micro vascular thrombi formation in various vessels and organs. The clotting factors are being used in the thrombi and as such there is not enough to prevent bleeding leading to consumption and utilisation of coagulation factors and proteins and potentially severe bleeding

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12
Q

List some clinical features of DIC

A

Severe bleeding, septic shock, renal failure, extensive bruising, blood in urine, thrombosis

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13
Q

What is the eitiology of DIC?

A

Massive tissue destruction/trauma, major surgeries, sepsis/ infection(bacteria infected tissues, endothelial injury due to toxins/ poisons or viruses, cancers. All these causes lead to the release of tissue factor and cause extensive coagulation and widespread micro vascular thrombi. Leads to ischaemia and consumption of platelets and consumption of factors.

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14
Q

Why is there an increase in fibrin degradation products?

A

Because there is increased consumption of factors for multiple thrombi. This means there will be more fibrin to break down and more FDPs

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15
Q

Can DIC be fatal?

A

Yes

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16
Q

Who is affected most by the acute type of immune thrombocytopenic purpura?

A

Children - usually result from a virus, illness (eg. Chicken pox) or after a vaccination

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17
Q

Who is affected most by the chronic type of immune thrombocytopenic purpura?

A

Mostly females in the 20-40years age bracket. Often is idiopathic but can be seen in association with other autoimmune disorders such as leukaemia, HIV etc.

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18
Q

Describe some clinical features of immune thrombocytopenic purpura?

A

Easy bruising, purpura, petechiae, nose bleeds, insidious / gradual onset, thrombocytopenia, large platelets, destroyed spleen

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19
Q

What is the pathogenesis of immune thrombocytopenic purpura?

A

Platelet antibodies usually IgG result in the premature removal of platelets from circulation by macrophages in the spleen. Then IgG antibodies are directed against the glycoprotein receptors IIb/IIIa and Ib on platelet membranes.

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20
Q

What is the normal lifespan of platelets?

A

7-10 days in ITP it is reduced to only hours

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21
Q

What are some laboratory findings you would see in Immune thrombocytopenic purpura?

A
  • Platelet count: decreased
  • In bone marrow there is normally increased immature megakaryocytes
  • In blood there is thrombocytopenia (decreased platelets) and the platelets that are there are giant
  • Sensitive tests to detect antibodies on the platelet surfaces or in the serum.
  • Bleeding time will be increased
  • Other haemostasis tests are normal
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22
Q

What are the main sources of vitamin K?

A

Fat soluble vitamin K is obtained from green vegetables and is synthesised by intestinal bacteria

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23
Q

List the aetiology / causes of vitamin K deficiency?

A
  • Inadequate Diet (vitamin K is in green leafy vegetables)
  • Malabsorption
  • Drugs can cause destruction of normal intestinal bacteria which normally produce vitamin K
  • Inhibition of vitamin K by drugs such as warfarin (decreased activity of factors II, VII, IX and X as well as Proteins C and S.
  • Liver disease,
  • Kidney disease
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24
Q

Clinical presentation for vitamin K deficiency?

A
  • Bleeding (mucosal and subcutaneous)
  • Ecchymoses a discoloration of the skin resulting from bleeding
  • Petechia a small red or purple spot caused by bleeding into the skin
  • Haematoma
  • In infants there can be birth defects of face, nose, bones and fingers vitamin K is poorly transferred from mother to infant via placenta as well as liver cell immaturity, lack of gut bacterial synthesis of the vitamin and low quantities in breast milk
  • Nose bleeds
  • Bleeding gums
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25
Q

What is the pathogenesis of vitamin K deficiency?

A

Vitamin K is responsible for the production in a number of factors in the coagulation cascade. Limited synthesis of factors II, VII, IX and X as well as Proteins C and S cause there to be defective coagulation cascade leading to prolonged bleeding

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26
Q

What would you expect to see in a lab results for vitamin K deficiency?

A
  • PT is prolonged no factor VII (has shortest half life)
  • Factor VII has the most significant suppression which is why only PT is affected (extrinsic pathway)
  • Decreased vitamin K
  • Platelet count and fibrinogen are normal but with absent fibrin degradation products as there is no fibrin being formed
27
Q

What factor is deficient in haemophilia A?

A

VIII

28
Q

What factor is deficient in haemophilia B?

A

IX

29
Q

What’s is the inheritance for haemophilia?

A

X linked. However 33% have no family history resulting from denovo mutations

30
Q

How much % activity of the factor IX and VIII doe mild, moderate and severe haemophiliacs shave?

A
  • Severe type is less than 1% factor VIII/ IX activity
  • Moderate is 1-5% factor VIII/IX activity
  • Mild is more than 5% factor VIII/IX activity
31
Q

Clinical features of haemophilia a/b?

A 
Clinical Features:
• Hemarthrosis (bleeding into Joints)
• soft tissue bleeds
• Excessive bruising 
• Muscle haematomas 
• Prolonged bleeding after dental work 
• Blood in urine 
• Local pressure ca cause entrapment neuropathy or Ischaemic necrosis 
• Clinical severity is related to how deficient factor 8/9 is
32
Q

Pathogenesis of haemophilia?

A

Deficiency of factor 8 or 9 leading to loss of the intrinsic pathway

33
Q

What would you do and expect to see in a lab results for haemophilia A/B?

A

Laboratory Results/diagnosis:
• Abnormal APTT
• Factor VIII/ IX assay to see how much there is
• Genetic testing for disorder
• Bleeding time and PT tests are normal as it affects intrinsic pathway

34
Q

Treatment for haemophilia?

A
  • Factor 8/9 replacement therapy
  • DDAVP (Desmopressin) increases the plasma factor 8 level in milder haemophiliacs only (following administration there is a 2-4 fold increase in factor 8)
35
Q

What is von Willebrand disease?

A
  • Reduced or abnormal function of von willebrand factor

* Most common inherited bleeding disorder affecting ~ 1% of the population

36
Q

Clinical features of von Willebrand disease?

A

Clinical features:
• Mucous membrane bleeding
• Menorrhagia
• Excessive blood loss from superficial cuts and abrasions
• Operative and post traumatic haemorrhages
• These abnormalities result in decreased platelet plug formation during the primary haemostatic response.
• Easy bruising
• Skin bleeding
• Prolonged bleeding form the Gums/GI tract/Uterus

37
Q

Causes / aetiology for von willebrands disease?

A
  • Autosomal dominant
  • Inherited VWD is caused by genetic mutations that lead to decreased impaired function of Von Willebrand Factor
  • Acquired: immunoproliferative cancer, Autoimmune Dz ( SLE)
38
Q

Pathogenesis of von willebrands disease?

A
  • Defective vWF which decreases platelet adhesion to collagen at injury site (no primary haemostatic plug formation)
  • Also carries factor 8 decrease in intrinsic pathway effectiveness
39
Q

What would you do and expect to see in a lab results for vw disease?

A 
Plasma VWF antigen level (VWF:Ag)
Plasma VWF activity
Factor VIII Activity
Platelet function analyzer assay
Bleeding time
  • poor platelet adhesion
  • Prolonged bleeding time
  • Decreased VWF
  • Often low factor VIII levels as it is bound to vWF
  • APTT May be prolonged
  • Defective platelet aggregation by patient plasma
  • Collagen binding function (of vWF to Collagen) is reduced
40
Q

Treatment for vw disease?

A

Desmopressin

VWF replacement

41
Q

What is thrombophilia?

A

Is the technical term for hypercoagulable state. Thrombosis (arterial or Venosus) is produced by a shift in the balance between procoagulant and profibrinolytic system (forming and breaking thrombus)

42
Q

Describe factor V Leiden?

A
  • Abnormal Factor V with activated protein C resistance (APC resistance)
  • Activated protein C promotes enzymatic degradation of factor VIIIa and Va
  • It is the most common cause of inherited thrombophilia (40-50%)
  • 5% of the population in Europe are heterozygous for factor V Leiden Mutation
  • This mutation is not present in black Africans, Chinese or Japanese populations
  • If there is a mutation in factor V (5) , protein C will not be able to inactivate it, meaning there will be more coagulation and thrombosis
43
Q

Describe protein c deficiency

A
  • Protein C is a vitamin K dependent protein that is synthesized in the liver
  • The primary effect of protein C is to inactivate coagulation factors Va and VIIIa
  • The inhibitory effect of protein C is greatly enhanced by protein S (another vitamin K dependent protein)
  • Heterozygous protein C deficiency is inherited in an autosomal dominant fashion
  • There is a Type I and Type II Protein C deficiency
  • Type I is decreased synthesis of normal protein
  • Type II is the production of an abnormally functioning protein
  • Protein C deficiency can cause Venous thromboembolisms and neonatal purpure fulminans in homozygous type (fatal)
  • Warfarin-induced skin necrosis can result in certain heterozygous teens or adults
44
Q

Describe protein S deficiency

A
  • Protein S is a vitamin K dependent glycoprotein
  • It is a cofactor for the protein C system
  • Only free form has activated protein C cofactor activity
  • In the presence of PS, activated protein C inactivates factors Va and VIIIa
45
Q

Describe anti thrombin III deficiency?

A
  • Autosomal dominant inheritance
  • Antithrombin III inactivates thrombin. Heparin increases ATIII activity
  • Quantitative and qualitative defects
  • Thrombotic phenomena in adolescence or even earlier
  • Frequently pulmonary embolism as first clinical manifestation
46
Q

What is hyperhompcyteinaemia?

A

A vitamin B12 deficiency (converts homocytein into cysteine in DNA) if there is no B12, normal DNA is not produced and there is excess homocytein

47
Q

List the clinical steps for diagnosing bleeding disorders?

A
  1. History:
    • Age, duration, spontaneous or induced, severity
    • H/O drug intake aspirin, warfarin
    • Family history
  2. Physical Exam:
    • Site of bleeding superficial or deep
    • Check skin/mucous membrane/intramuscular joints
  3. Lab:
    • Platelet count, PT,aPTT &TT, bleeding time
    • Factor Assay ,anticoagulants, platelet function studies and thromboelastogram (rarely)
48
Q

State the normal platelet count

A

140-400 x 10^9

49
Q

What 2 things can inherited thrombophilia be due to?

A

1.a deficiency of natural anticoagulant
(such as protein C, protein S or antithrombin)

  1. Amutation in a clotting factor, making it resistant to inhibiton (factor V Leiden) or resistant to fibrinolysis
50
Q

What does PT test?

A

Extrinsic & common pathway (7+2,5,10), prolonged in acquired diseases , liver disease, warfarin therapy

51
Q

What does aPTT test?

A

intrinsic and common pathway (8,9,12,+2,5,10), haemophilia, congenital bleeding disorders

52
Q

What does TT test?

A

Fibrinogen (common pathway), DIC, HUS,TTP and heparin therapy

53
Q

What’s factors does thrombin activate to amplify the coag pathway?

A

VIIIA and V

54
Q

List the 3 natural coagulation Inhibitors ( anticoagulants)

A

ATIII, protein C & S

55
Q

List the 4 routine tests for haemostasis

A

PLT count, PT, APTT, TT

56
Q

Describe Hemolytic Uremic Syndrome

A 
• Childhood & Adult type.
• Normal ADAMTS13 levels
• Platelet activation secondary to endothelial damage (microangiopathy)
• Childhood HUS: 
• Associated with E.coli or Shigella Shiga toxin. 
• Glomerular damage - predominant.
• Seizures common
• Adult HUS: 
• Shigella, inherited or drugs.
• Inappropriate activation of 
complement, endothelial damage.
57
Q

Describe Thrombotic thrombocytopenic purpura

A
  • Widespread thrombosis with Thrombocytopenia, Red Cell fragmentation, Fever, Transient Neurologic deficits & Kidney failure.
  • Deficiency of ADAMTS13 a metalloprotease which normally breaks down vWF multimers to stop platelet activation.
  • Deficiency leads to excess vWF unchecked plt adhesion & aggregation thrombosis & plt.
  • Acquired: Antibody to ADAMTS13 deficiency.
  • Congenital: Mutation deficiency of ADAMTS13.
  • Treat: plasma exchange with FFP or Cryoprecipitate to remove antibody and replace ADAMTS13
58
Q

What is Virchows triangle?

A

Describes the three broad categories of factors that are thought to contribute to thrombosis : abnormal blood flow, endothelial injury or hypercoagulable state

59
Q

What are some examples/ causes of endothelial damage leading to thrombosis?

A
  • trauma or surgery
  • atherosclerosis in vessel
  • chemical irritation (eg. Smoking)
  • Heart valve disease or replacement
  • Hypertension
  • Indwelling catheters
60
Q

What are some examples/causes of altered blood flow leading to thrombosis?

A
  • Atrial fibrillation
  • Left ventricle dysfunction
  • Immobility or paralysis (be bound stasis of blood flow)
  • Venous insufficiency or varicose veins
  • Venous obstruction tumour that obstructs flow coming back from heart
  • Pregnancy
61
Q

Describe briefly anti phospholipid syndrome

A

Antiphospholipid syndrome (APS), also known as antiphospholipid antibody syndrome and sometimes Hughes syndrome, is a disorder characterized by elevated levels of multiple different antibodies that are associated with both arterial and venous thrombosis (clots in the arteries and veins).

There are two primary classes of antiphospholipid (aPL) antibodies, the antibodies associated with APS. These are called anticardiolipin antibodies and the lupus anticoagulant, and are directed against specific molecules. These aPL antibodies appear to be mainly directed against two particular molecules: beta-2-glycoprotein I (ß2GPI, a normal protein found in the blood whose function is unknown) and another molecule known as prothrombin (a normal blood protein that binds to phospholipids and plays a very important role in blood clotting).

  • Lupus AC is an antibody that causes prolongation of aPTT
  • These patients have a risk of clotting
  • Can be without autoimmune disorder or with an autoimmune disorder
  • Have unusual sites of venous and arterial thrombosis
  • Also have thrombocytopenia
62
Q

What are the differences between a thrombus and a post mortem clot?

A
  • Thrombus is firm and attached to vessel wall

* Post mortem clot is friable and not attached to vessel wall

63
Q

What are the pharmacological and non pharmacological ways to manage a thrombus?

A
  • Non pharmacological - DVT prophylaxis, early mobilization, pressure stockings, keeping well hydrated and exercise
  • Pharmacological anticoagulation - heparin , warfarin , NOAC
64
Q

What are some qualities of a good anticoagulant?

A
  • Oral active
  • Fixed dosing
  • Favourable therapeutic index don’t clot OR bleed
  • Prevention of inappropriate thrombosis
  • Low bleeding risk
  • No interactions (food or with other drugs)
  • Easy to monitor
  • Reversible

MD2011 (32 decks)

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