Other Disorders of Hemostasis Pathology Study Guide

Other Disorders of Hemostasis Pathology Video

Heparin Induced Thrombocytopenia

Heparin induced thrombocytopenia is the destruction of platelets that results from heparin therapy.

Heparin induced thrombocytopenia (HIT) is an immune complication due to antibodies directed against complexes containing heparin and a platelet factor 4 (PF4).

Platelet fragments could activate remaining platelets and cause thrombosis.

Never give heparin to a patient that has experienced heparin induced thrombocytopenia (HIT).

Status post recent amputation of the right leg; ongoing necrosis of the left leg despite amputation 5 days before. Heparin-induced thrombocytopenia in a non-heparin-naive patient: a case report. Wiegele M, Adelmann D, Gratz J, Schaden E - SpringerPlus (2015). Not Altered. CC.
Heparin Induced Thrombocytopenia. Molecular structure of argatroban, a direct thrombin inhibitor used as an alternative to heparin in HIT Fvasconcellos (talk · contribs) Not altered. Public Domain
Heparin Induced Thrombocytopenia. A schematic drawing of platelet factor 4, which when bound to heparin leads to an immune response in HIT. - Not altered. Public Domain
Histological examination of aspirated thrombi. a. High-power (original magnification 400×) microphotograph showing the infiltration of inflammatory cells in aspirated fibrin-rich thrombus as observed after haematoxylin and eosin staining. b. High-power (original magnification 400×) microphotograph showing the eosinophilic infiltration as observed after Giemsa staining (between arrowheads). Stent thrombosis caused by metal allergy complicated by protein S deficiency and heparin-induced thrombocytopenia: a case report and review of the literature. Konishi T, Yamamoto T, Funayama N, Yamaguchi B, Sakurai S, Nishihara H, Yamazaki K, Kashiwagi Y, Sasa Y, Gima M, Tanaka H, Hotta D, Kikuchi K - Thrombosis journal (2015). Not Altered. CC.

Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) is due to the activation of the coagulation cascade by pathology.

Ischemia and infarction are brought on by widespread microthrombi.

Bleeding is caused by factors and platelet consumption.

Mucosal bleeding is a common symptom of disseminated intravascular coagulation (DIC).

Disseminated intravascular coagulation (DIC) is usually accompanied by another medical issue such as:

The majority of the time DIC is due to another disease process.

Obstetric complications in which the amniotic fluid’s tissue thromboplastin initiates coagulation
Endotoxins from the bacterial wall and macrophage derived cytokines (such as tumor necrosis factor (TNF) and interleukin-1 (IL-1)) cause endothelial cells to produce tissue factors in sepsis (particularly with E. Coli or N. meningitidis)
Coagulation gets activated by adenocarcinoma mucin
Primary granules in acute promyelocytic leukemia (APL)
Coagulation activated by rattlesnake venom

Laboratory findings of disseminated intravascular coagulation (DIC) include:

Decreased platelet count
Decreased fibrinogen
Increased PT
Increased PTT
Increased INR
Increased D-dimer
Peripheral smear showing helmet cells and schistocytes

Elevated fibrin split products are present, especially D-dimer.

The best screening test for disseminated intravascular coagulation (DIC) is elevated D-dimer.

The D-dimer is from splitting of cross-linked fibrin.

The D-dimer is not derived from splitting of fibrinogen.

Treatment of disseminated intravascular coagulation (DIC) includes:

Addressing the underlying cause as well
Transfusing cryoprecipitate (contains coagulation factors) and blood products if clinically indicated

Disseminated intravascular coagulation. Arrows indicate intravascular fibrin deposition. Clinical review: molecular mechanisms underlying the role of antithrombin in sepsis. Wiedermann CJ - Critical care (London, England) (2006). Not Altered. CC.
Other Disorders of Hemostasis. Very high magnification micrograph of acute thrombotic microangiopathy, abbreviated TMA. Kidney biopsy. PAS stain. The differential diagnosis of TMA includes:[1] Hemolytic uremic syndrome (HUS). Thrombotic thrombocytopenic purpura (TTP). HIV associated TTP. Disseminated intravascular coagulation (DIC). Malignant hypertension. Scleroderma renal crisis. Antiphospholipid antibody syndrome (APLA). Drug toxicity, e.g. calcineurin inhibitor toxicity. Related images High mag. Very high mag. High mag. Very high mag. Another case - with chronic changes: Intermed. mag. High mag. Very high mag. References (May 2010). "Thrombotic microangiopathy: new insights.". Curr Opin Nephrol Hypertens 19 (3): 242-7. DOI:10.1097/MNH.0b013e3283378f25.Nephron. Not altered. CC BY-SA 3.0
Disseminated Intravascular Coagulation. Pathophysiological considerations in the clinical presentation of DIC. Systemic activation of coagulation together with cellular activation (endothelial cells, neutrophils, and platelets) leads to excessive thrombin generation and its functional consequences.Abbreviations: FDP, fibrin degradation products; NETs, neutrophil extracellular traps; PAR, protease-activated receptor. Current Pathological and Laboratory Considerations in the Diagnosis of Disseminated Intravascular Coagulation. Annals of Laboratory Medicine. Not altered. CC.

Disorders of Fibrinolysis

After the injured vessel heals, the thrombus is removed by normal fibrinolysis.

Plasminogen is transformed into plasmin by tissue plasminogen activator (TPA).

Plasmin breaks down coagulation components, degrades serum fibrinogen and fibrin, and prevents platelet aggregation.

Plasmin is deactivated by alpha2-antiplasmin (a2AP).

Plasmin overactivity, which results in increased cleavage of serum fibrinogen, is the cause of fibrinolysis disorders.

Examples of plasmin overactivity include:

Radical prostatectomy due to release of urokinase causes plasmin to be activated
Reduced synthesis of alpha2-antiplasmin (a2AP) due to liver cirrhosis
Increases hemorrhage while presenting (resembles disseminated intravascular coagulation (DIC))

Laboratory findings in disorders of fibrinolysis include:

Increased PT
Increased PTT
Increased bleeding time
Increased fibrinogen split products without elevated D-dimer
Normal platelet count

Plasmin destroys coagulation factors and blocks platelet aggregation.

Treatment is aminocaproic acid which prevents plasminogen activation.

Fibrinolysis suppression in sepsis. Microorganisms, their products, and endogenous inflammatory mediators may lead to hypofibrinolysis by enhancing the release of plasminogen activator inhibitors (mainly PAI-1), particularly by endothelial cells. The same agents may variably influence the release of t-PA (see text for further details). Sepsis-associated disseminated intravascular coagulation and thromboembolic disease. Semeraro N, Ammollo CT, Semeraro F, Colucci M - Mediterranean journal of hematology and infectious diseases (2010). Not Altered. CC.