Project: Ghana Emergency Medicine Collaborative
Document Title: Hemostasis: Platelet and Coagulation Disorders
Author(s): ...
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Hemostasis:	
  	
  
Platelet	
  and	
  Coagula4on	
  Disorders	
  

3	
  
 
	
  

vasculature
Kelvinsong,	
  Wikimedia	
  Commons	
  

platelets

Tleonardi,	
  Wikimedia	
  Commons	
  

coagulatio...
Steinsky,	
  Wikimedia	
  Commons	
  

5	
  
Source	
  undetermined	
  

6	
  
¡ 

Mediated by tissue factors

¡ 

Affords a rapid response

¡ 

Prolonged prothrombin time (PT)

¡ 

Involves factor...
¡ 

Mediated by surface contact factors

¡ 

Slower responder

¡ 

Prolonged partial thromboplastin time (aPTT)

¡ 

I...
¡ 

Prolonged PT and aPTT

¡ 

Thrombin and fibrinogen form insoluble clot

9	
  
¡ 
¡ 
¡ 
¡ 
¡ 

Thrombocytopenia = platelet count < 100,000 cu mm
Platelet count < 50,000 variable risk
Platelet coun...
UBC	
  Dermatology	
  

11	
  
Source	
  undetermined	
  
12	
  
¡ 

Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

¡ 

Thrombotic Thrombocytopenic Purpura (TTP)

¡ 

Hemolytic-Ur...
¡ 

Acquired autoimmune disorder
§  Thrombocytopenia with normal bone marrow

¡ 

Acute form
§  Children 2-6 yrs. old
...
¡ 

Chronic form
§  Adults: women > men or women < men
§  Associated with autoimmune disorder (SLE, HIV)
§  Resolution...
Source	
  undetermined	
  
16	
  
¡ 

Management
§  Do not transfuse platelets
§  Steroids
§  Splenectomy
§  Immunoglobulin therapy
§  Plasmapheresis
...
¡ 

Thrombocytopenia + microangiopathic hemolytic anemia

¡ 

Classic pentad §  Fever, anemia, thrombocytopenia, renal ...
¡ 

Laboratory findings
§  Schistocytes (helmet cells)

▪  Intravascular hemolysis – peripheral smear
§  Platelets < 20...
Wadsworth	
  Center	
  

20	
  
Source	
  undetermined	
  
21	
  
¡ 

Thrombocytopenia + microangiopathic hemolytic
anemia + acute renal failure

¡ 

Primarily in children 6 mo – 4 yr
§...
¡ 

Presentation – bloody diarrhea and seizure
§  Pentad of TTP
§  TTP – neurologic symptoms more pronounced
§  HUS – ...
¡ 

Treatment
§  Supportive, dialysis (?), do not administer antibiotics.

Schistocytes + child = HUS
Schistocytes + adu...
¡ 

Type I
§  Platelet count rarely < 100,000
§  Occurs within first few days
§  Benign – not associated with thrombos...
¡ 

Type II
§  Autoimmune and consumptive
§  Occurs day 4-14
§  1/3 of cases associated with thrombosis
§  Must d/c h...
¡ 

Most common
§  Quinidine / quinine, sulfonamides. Phenytoin, ASA

¡ 

Less common
§  Chronic EtOH, NSAID’s (indome...
¡ 

Hemophilia A (classic hemophilia)

¡ 

Hemophilia B (Christmas disease)

¡ 

Disseminated Intravascular Coagulation...
¡ 
¡ 
¡ 

X-linked recessive bleeding disorder due to
deficiency of factor VIII function
Spontaneous genetic mutations ...
¡ 

Severe – spontaneous bleeding
§  < 1% factor VIII activity

¡ 

Moderate – occasional spontaneous bleeding but
more...
¡ 

90% of bleeding events involve
§  Joints – knee involvement > 50%
§  Intramuscular – neuro-vascular compromise poss...
¡ 

Laboratory findings
§  PTT increased unless > 30% factor activity present
§  Specific factor assays necessary
§  I...
¡ 

Treatment
§  Recombinant factor VIII – therapy of choice - $$$$$

▪  each IU/kg increases factor VIII by 2%
§  Fact...
¡ 

Treatment (cont)
§  Fresh frozen plasma contains one IU/ml of factor VIII

▪  250 ml/bag

[14 bags = 3500ml]

§  Cr...
¡ 

X-linked recessive bleeding disorder due to
deficiency of factor IX function

¡ 

Classification is same as Hemophil...
¡ 

Treatment
§  Recombinant factor IX, if available
§  Factor IX concentrate (pooled = infection risk)
§  Both factor...
¡ 

Consumptive coagulopathy – hemostasis gone wild

¡ 

Simultaneous coagulation and fibrinolytic pathways
promoting bo...
¡ 

Laboratory –
§  PT elevated, PTT often elevated
§  Decreased platelets, fibrinogen
§  Increased fibrin split produ...
¡ 

Treatment
§  Supportive aggressive resuscitation

▪  IV fluids and RBC transfusion
§  Fresh frozen plasma to replac...
¡ 

Most common inherited bleeding disorder

¡ 

von Willibrand’s factor (vWF) facilitates platelet
adhesion to each oth...
¡ 

Type I
§  Mild form = 80% of patients
§  Mucosal bleeding – decrease in vWF (quantitative)

¡ 

Type II

§  Mild ...
¡ 

Treatment
§  Desmopressin (DDAVP) – stimulates endothelial cells

to secrete stored vWF
▪  0.3 microgram / kg IV or ...
¡ 

Warfarin
§  Vitamin K 1.0-2.5 mg po
▪  10 mg slow IV for severe hemorrhage
§  Fresh frozen plasma 2-4 units
▪  4-6 ...
¡ 

Protamine sulfate
§  1 mg per 100 units of infused heparin in previous 4 hrs

IV over 10 min (no more than 50 mg)
¡...
¡ 
¡ 
¡ 
¡ 
¡ 

Cryoprecipitate 10 units IV
Fresh frozen plasma 2 units IV
Platelet transfusion 6 units IV (?)
Aminoc...
¡ 
¡ 
¡ 
¡ 

Vitamin K 10 mg SC or IV
Fresh frozen plasma 10-25 ml / kg
Platelet transfusion
Desmopressin (DDAVP)
§  ...
¡ 
¡ 

Hemodialysis provides transient benefit to platelet
function for 24 – 48 hrs
Desmopressin (DDAVP)
§  0.3 microgr...
¡ 

ASA, NSAID’s, clopidogrel (Plavix), ticlopidine (Ticlid)
§  All inhibit platelet aggregation

¡ 
¡ 
¡ 

Discontin...
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GEMC- Hemostasis: Platelet and Coagulation Disorders- Resident Training

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This is a lecture by Dr. Joseph Hartmann from the Ghana Emergency Medicine Collaborative. To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc. Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/.

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GEMC- Hemostasis: Platelet and Coagulation Disorders- Resident Training

  1. 1. Project: Ghana Emergency Medicine Collaborative Document Title: Hemostasis: Platelet and Coagulation Disorders Author(s): Joseph H. Hartmann (University of Michigan), DO 2012 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. These lectures have been modified in the process of making a publicly shareable version. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/privacy-and-terms-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers. 1  
  2. 2. Attribution Key for more information see: http://open.umich.edu/wiki/AttributionPolicy Use + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation License Make Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair. 2  
  3. 3. Hemostasis:     Platelet  and  Coagula4on  Disorders   3  
  4. 4.     vasculature Kelvinsong,  Wikimedia  Commons   platelets Tleonardi,  Wikimedia  Commons   coagulation pathway GrahamColm,  Wikimedia  Commons   4  
  5. 5. Steinsky,  Wikimedia  Commons   5  
  6. 6. Source  undetermined   6  
  7. 7. ¡  Mediated by tissue factors ¡  Affords a rapid response ¡  Prolonged prothrombin time (PT) ¡  Involves factors II, VII, IX, and X §  Vitamin K dependent (coenzyme) ¡  Inhibition of vitamin K with warfarin 7  
  8. 8. ¡  Mediated by surface contact factors ¡  Slower responder ¡  Prolonged partial thromboplastin time (aPTT) ¡  Involves factors VIII, IX, and XI §  Accounts for 99% of inherited bleeding disorders ▪  Hemophilia A – factor VIII ▪  Hemophilia B – factor IX ▪  Hemophilia C – factor XI 8  
  9. 9. ¡  Prolonged PT and aPTT ¡  Thrombin and fibrinogen form insoluble clot 9  
  10. 10. ¡  ¡  ¡  ¡  ¡  Thrombocytopenia = platelet count < 100,000 cu mm Platelet count < 50,000 variable risk Platelet count < 20,000 transfusion appropriate Platelet count < 10,000 spontaneous hemorrhage Platelet dysfunction = mucus membrane bleeding §  Epistaxis §  Gingival §  Vaginal bleeding §  Petechiae, purpura 10  
  11. 11. UBC  Dermatology   11  
  12. 12. Source  undetermined   12  
  13. 13. ¡  Immune (Idiopathic) Thrombocytopenic Purpura (ITP) ¡  Thrombotic Thrombocytopenic Purpura (TTP) ¡  Hemolytic-Uremic Syndrome (HUS) ¡  Heparin –Induced Thrombocytopenia (HIT) ¡  Drug-Induced Inactivation of Platelets 13  
  14. 14. ¡  Acquired autoimmune disorder §  Thrombocytopenia with normal bone marrow ¡  Acute form §  Children 2-6 yrs. old §  Associated with prior viral illness (<3 wk) §  Resolution > 1-2 months, often quite longer §  Spontaneous resolution in 90% 14  
  15. 15. ¡  Chronic form §  Adults: women > men or women < men §  Associated with autoimmune disorder (SLE, HIV) §  Resolution is rare §  Thrombocytopenia < 20,000 §  Mucosal bleeding 15  
  16. 16. Source  undetermined   16  
  17. 17. ¡  Management §  Do not transfuse platelets §  Steroids §  Splenectomy §  Immunoglobulin therapy §  Plasmapheresis 17  
  18. 18. ¡  Thrombocytopenia + microangiopathic hemolytic anemia ¡  Classic pentad §  Fever, anemia, thrombocytopenia, renal failure, neurologic symptoms ¡  Associations – §  Autoimmune – AIDS, lupus, scleroderma, Sjogren §  Pregnancy §  Rx – cyclosporine, tacrolimus, quinidine 18  
  19. 19. ¡  Laboratory findings §  Schistocytes (helmet cells) ▪  Intravascular hemolysis – peripheral smear §  Platelets < 20,000 §  Increased reticulocyte count §  Increased indirect bilirubin §  Increased LDH §  Decreased haptoglobin ¡  Tx: urgent hematology consult, plasmapheresis, steroids 19  
  20. 20. Wadsworth  Center   20  
  21. 21. Source  undetermined   21  
  22. 22. ¡  Thrombocytopenia + microangiopathic hemolytic anemia + acute renal failure ¡  Primarily in children 6 mo – 4 yr §  Most common cause of acute renal failure in children ¡  Associations – §  E. coli H7:0157 Shiga-like toxin 22  
  23. 23. ¡  Presentation – bloody diarrhea and seizure §  Pentad of TTP §  TTP – neurologic symptoms more pronounced §  HUS – renal dysfunction more pronounced ¡  Laboratory findings §  SCHISTOCYTES §  TTP lab findings §  Worse renal function parameters, i.e. renal failure 23  
  24. 24. ¡  Treatment §  Supportive, dialysis (?), do not administer antibiotics. Schistocytes + child = HUS Schistocytes + adult = TTP Schistocytes + neurologic dysfunction = TTP Schistocytes + renal dysfunction = HUS 24  
  25. 25. ¡  Type I §  Platelet count rarely < 100,000 §  Occurs within first few days §  Benign – not associated with thrombosis §  Platelet count normalizes regardless of heparin use / disuse 25  
  26. 26. ¡  Type II §  Autoimmune and consumptive §  Occurs day 4-14 §  1/3 of cases associated with thrombosis §  Must d/c heparin No LMW heparins §  No platelet transfusions unless life-threatening bleeding §  Treat with direct thrombin inhibitors ▪  Hirudin (Revasc) ▪  Lepirudin (Refludan) ▪  Argatroban (Novastan) 26  
  27. 27. ¡  Most common §  Quinidine / quinine, sulfonamides. Phenytoin, ASA ¡  Less common §  Chronic EtOH, NSAID’s (indomethacin), valproic acid ¡  Development of antiplatelet antibodies ¡  Treatment §  Recovery within one week §  Steroids §  DDAVP / platelet transfusions for severe hemorrhage 27  
  28. 28. ¡  Hemophilia A (classic hemophilia) ¡  Hemophilia B (Christmas disease) ¡  Disseminated Intravascular Coagulation ¡  von Willibrand’s Disease ¡  Medication toxicity 28  
  29. 29. ¡  ¡  ¡  X-linked recessive bleeding disorder due to deficiency of factor VIII function Spontaneous genetic mutations occur accounting 1/3 of new cases Severity of disease dependent on % factor VIII activity function §  Classified as mild, moderate, severe 29  
  30. 30. ¡  Severe – spontaneous bleeding §  < 1% factor VIII activity ¡  Moderate – occasional spontaneous bleeding but more commonly follows trauma / surgery §  1% - 5% factor VIII activity ¡  Mild – occasional hemorrhage after dental extractions, menses §  >5% factor VIII activity 30  
  31. 31. ¡  90% of bleeding events involve §  Joints – knee involvement > 50% §  Intramuscular – neuro-vascular compromise possible ¡  ¡  ¡  ¡  Bleeding manifestations can be delayed for hours – though normally seen within 8 hrs Minor lacerations and abrasions not normally problematic Head injuries are treated without waiting for CT Believe the patient ! 31  
  32. 32. ¡  Laboratory findings §  PTT increased unless > 30% factor activity present §  Specific factor assays necessary §  Inhibitor may be present in 10-25% of patients ▪  Antibody against factor VIII 32  
  33. 33. ¡  Treatment §  Recombinant factor VIII – therapy of choice - $$$$$ ▪  each IU/kg increases factor VIII by 2% §  Factor VIII concentrate –pooled donors (infection risk) §  Major life-threatening bleeding 50 IU/kg initially §  Hemarthrosis / muscle bleeding 25-50 IU/kg §  Minor bleeding 12.5 – 25 IU/kg §  Desmopressin (DDAVP) – mild to moderate disease ▪  Stimulates increase of functional factor VIII by 3-5 fold ▪  Onset 30 min; dose 0.3 microgram/kg IV 33  
  34. 34. ¡  Treatment (cont) §  Fresh frozen plasma contains one IU/ml of factor VIII ▪  250 ml/bag [14 bags = 3500ml] §  Cryoprecipitate contains 100 IU of factor VIII per bag ▪  80-100 ml bag [35+ bags = 3500ml] §  FFP and/or cryoprecipitate should be used only as temporizing measures if recombinant or concentrate factor VIII not available ¡  Get a consulting hematologist on board early to direct treatment choices and dosing. 34  
  35. 35. ¡  X-linked recessive bleeding disorder due to deficiency of factor IX function ¡  Classification is same as Hemophilia A ¡  Clinical presentation is same as Hemophilia A ¡  Inhibitor to factor IX found < 2% of patients 35  
  36. 36. ¡  Treatment §  Recombinant factor IX, if available §  Factor IX concentrate (pooled = infection risk) §  Both factor products increase factor IX by 1% for each IU/kg §  Fresh frozen plasma contains 1 IU/ml of factor IX §  Cryoprecipitate - no factor IX §  Desmopressin (DDAVP) ineffective 36  
  37. 37. ¡  Consumptive coagulopathy – hemostasis gone wild ¡  Simultaneous coagulation and fibrinolytic pathways promoting both bleeding and thrombotic components – one predominates ¡  Etiology: §  Infection – most common, esp. gram neg sepsis §  Carcinoma / leukemia §  Trauma, hepatic dz, pregnancy, ARDS, viper envenom- ation, transfusion reaction 37  
  38. 38. ¡  Laboratory – §  PT elevated, PTT often elevated §  Decreased platelets, fibrinogen §  Increased fibrin split products and d-dimer (more specific, less sensitive) §  Fragmented RBC’s anemia 38  
  39. 39. ¡  Treatment §  Supportive aggressive resuscitation ▪  IV fluids and RBC transfusion §  Fresh frozen plasma to replace coagulation factors ▪  Two units at a time §  Cryoprecipitate for fibrinogen replacement ▪  Ten bags §  Platelet transfusion §  Heparin if thrombosis predominates ▪  Ca, leukemia, pregnancy-related §  Activated protein C, if septic shock 39  
  40. 40. ¡  Most common inherited bleeding disorder ¡  von Willibrand’s factor (vWF) facilitates platelet adhesion to each other and to damaged endothelium §  Also, a carrier protein for factor VIII ¡  Three forms of clinical presentation ¡  Laboratory – usually normal PT and PTT; bleeding time prolonged; vWF activity low 40  
  41. 41. ¡  Type I §  Mild form = 80% of patients §  Mucosal bleeding – decrease in vWF (quantitative) ¡  Type II §  Mild form =10% of patients §  Mucosal bleeding – dysfunctional vWF (qualitaitve) ¡  Type III §  Severe form =10% of patients §  Bleeding episodes resemble hemophilias – no detectable vWF 41  
  42. 42. ¡  Treatment §  Desmopressin (DDAVP) – stimulates endothelial cells to secrete stored vWF ▪  0.3 microgram / kg IV or SC over 30 min q 12 hr ▪  Concentrated intranasal form ▪  1 spray in one nostril (150 micrograms) in children > 5 y/o ▪  1 spray each nostril (300 micrograms) in adolescent / adult §  Factor VIII concentrates 20-30 IU/kg for nonresponder Type I or Type II and III §  Cryoprecipitate 1-2 bags / 10 kg 42  
  43. 43. ¡  Warfarin §  Vitamin K 1.0-2.5 mg po ▪  10 mg slow IV for severe hemorrhage §  Fresh frozen plasma 2-4 units ▪  4-6 units for severe hemorrhage §  Prothrombin complex concentrate ▪  8.8 units/kg IV up to 500 units §  Recombinant factor VIIa (NovoSeven) ▪  15-20 micrograms / kg IV over 3-5 min 43  
  44. 44. ¡  Protamine sulfate §  1 mg per 100 units of infused heparin in previous 4 hrs IV over 10 min (no more than 50 mg) ¡  Low molecular weight heparin (partial reversal) §  1 mg per 1 mg of enoxaparin §  1 mg per 100 anti-Xa units of dalteparin 44  
  45. 45. ¡  ¡  ¡  ¡  ¡  Cryoprecipitate 10 units IV Fresh frozen plasma 2 units IV Platelet transfusion 6 units IV (?) Aminocaproic acid (Amicar) 6 mg IV or po q 4hr Recombinant factor VIIa (NovoSeven) §  40-160 micrograms / kg IV over 1-2 min 45  
  46. 46. ¡  ¡  ¡  ¡  Vitamin K 10 mg SC or IV Fresh frozen plasma 10-25 ml / kg Platelet transfusion Desmopressin (DDAVP) §  0.3 microgram / kg SC or §  0.3 microgram / kg in 50 ml NS IVPB over 30 min ¡  Cryoprecipitate if fibrinogen levels < 100 mg/dl 46  
  47. 47. ¡  ¡  Hemodialysis provides transient benefit to platelet function for 24 – 48 hrs Desmopressin (DDAVP) §  0.3 micrograms / kg in 50 ml NS IVPB over 30 min ¡  ¡  Platelet transfusion Cryoprecipitate 47  
  48. 48. ¡  ASA, NSAID’s, clopidogrel (Plavix), ticlopidine (Ticlid) §  All inhibit platelet aggregation ¡  ¡  ¡  Discontinue agent Platelet transfusion Desmopressin (DDAVP) §  0.3 micrograms / kg in 50 ml NS IVPB over 30 min 48  

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