Mathematical Models for Blood Coagulation - Fluid-Structure Interaction and Biomedical Applications - page 498

Plasminogen, synthesized by the liver, is available in circulating blood, so it is
naturally trapped in the clot. We know that it is activated to Plasmin by the serine
proteases tPA and urokinase (and also by Kallikrein and FXIIa). We recall that
plasmin and plasminogen activators have their own serpins, making sure that those
proteases are eliminated once they have performed their task. We have seen that
TAFI, accumulated during clot formation, reduces plasmin action, retarding the pro-
cess. Secretion of additional tPA by the endothelium is stimulated by the clot itself.
At the early stage of fibrinolysis fragments of the fibrin network may recombine.
A product of fibrin degradation is the so-called D-dymer , whose presence in
blood reveals ongoing thrombosis.

7.5 Bleeding Disorders

There are two classes of coagulopathies :

(1) hypocoagulability , generally with bleeding diathesis , i.e., spontaneous

bleeding,
(2) hypercoagulability or thrombophilia , producing thrombosis.

Such phenomena can occur with different levels of intensity and consequently with a
different impact on health. This is largely an open field for mathematical modeling.
We can review bleeding disorders according to their origin. So a natural way of
exposing this material is to follow the same articulation as Sect. 7.3 .

7.5.1 Platelet-Related Bleeding Disorders

Since platelets are so complicated there are several types of dysfunctions that may
produce bleeding disorders.

• Thrombocytopenia Literally it means scarcity of thrombocytes (i.e., platelets).

It is diagnosed if the platelet count drops below 1/3 of the minimum (i.e., less
than 50;000=mm 3 ). There are very many possible causes of different gravity.
For instance, the spleen may start storing too many platelets, sequestering them
from the bloodstream, or the immune system may produce antibodies attacking
platelets ( Immune Thrombocytopenia ), or it can be related to other pathological
conditions. It can also be drug induced. A striking and puzzling example in the
latter class is

- Heparin-Induced Thrombocytopenia (HIT). Thrombotic episodes (also of a

massive character) were observed in patients under anticoagulant treatments
with heparin. This counterintuitive phenomenon has been the object of many
controversial studies. Today it is believed to result from an immune reaction
triggered by heparin, which induces platelets activation and clustering. We
recommend the reading of [ 128 ].