Streptokinase in Prostatitis Treatment STREPTOKINASE AS PLASMINOGEN ACTIVATION INHIBITOR FOR CHLAMYDIAL PROSTATITIS  PATIENTS Pavels Ivdra, Gunars Purmalis, Aija Zilevica, Ivars Geldners, Janis Zalkalns, Inara Ancupane, Alfreds Miltins Riga Clinical Hospital No.7, Head doctor: E. Platkajis Latvian Association of Physicians - Chlamydiologists					Pavels Ivdra
Gunars Purmalis	Aija Zilevica	Ivars Geldners	Janis Zalkalns	Inara Ancupane	Alfreds Miltins

Streptokinase (SK) may have a double enzymatic pharmacokinetic effect.First of all, SK is a plasminogen activator which is needed in thrombolytic therapy. In 1933 Tillet and Garner [1] were the first to discover the potency of pure culture hemolytic streptococcal filtrate to lyse human plasma clots containing fibrinogen and thrombin. In 1945, Christensen and Macleod ascertained that the above-mentioned bacterial factor, which was suggested to be named - streptokinase, was acting as plasminogen activator [2]. But streptokinase may have an opposite, antagonistic role as well, acting as an inhibitor (inactivator) of plasminogen activation.

Blood plasma proteins are known to contain plasmin inhibitors (inactivators). Already in 1968 the biochemists Werle E., Trautschold I., Haendle H., Fritz H. had published, that inhibitors,by forming protein compound complexes, with streptokinase (SK) involved into them , it loses its catalytic activity on plasminogen [3].

Inhibition (inactivation) of fibrinolytic activity is clinically manifest as a secondary induced hypercoagulaemia and hyperfibrinogenaemia with side-effects even 6-9 hrs. after SK i/v infusion. Since 1981, while working with fibrinolytic enzymes, we had observed a SK side-effect, so far having been unknown to clinicians, which expressed itself as an inhibition of blood fibrinolytic activity and it made physicians refuse from SK or treat by urokinase and t-PA [4,5,6].

For chronic prostatitis, paraprostatitis and other urogenital chlamydiosis patients, the effect of SK on the fibrinolytic enzyme system is not one-sided. SK is characteristic of 3 antipodal types of activity:

1) resistance to plasminogen activation,
2) fibrinolytic inhibitor's properties exposed as a secondary induced hypercoagulaemia and hyperfibrinogenaemia
3) high sensitivity of plasminogen activation with a fibrinolytic effect with SK given in small doses and even at a high antistreptokinase titre [7,8,9].

Within the last 3 years, 286 chronic prostatitis patients had undergone treatment at the Urology Department of the Clinical Hospital "Gaiļezers", in 37 cases (13%), a secondary induced hypercoagulaemia with a danger to thrombembolic complications was diagnosed if the enzyme therapy with SK were continued.

What to do in such cases? What action to take? For the sake of prevention of anaphylactic complications, it was important to open the blocked plasminogen activation centre. It was performed by using urokinase or tissue plasminogen activator (t-PA) Actilyse in the dosage taking into account the plasma euglobulin fraction during fibrinolysis. After that the enzyme therapy may be continued with SK.

Enzyme preparation SK of microbiological origin is the cheapest plasminogen activator and is available to indigent patients [10,11[12] as well.

Clinical Case 1.
(Case history Nr. 14756-99; Nr. 2918-2000)

Patient K.S., 47 yrs.old, hospitalized in the Urology Department due to an acute orchitis, chlamydial prostatitis, paraprostatitis, inflammation of urogenital venous plexus (phlebothrombosis of small pelvis), hypercoagulaemia and hyperfibrinogenaemia. Fibrinogen concentration in the blood 13,8 g/l, spontaneous fibrinolysis 1% (norm 10-15%).

For prevention of serious thrombolytic complications, the patient was given streptokinase in increasing doses from 6000-500 000 e.u. for 16 days, in combination with 2.830 000 e.u.Allergic reactions and arthralgias did not allow to increase the streptase doses quicker. SK had lost its catalytic activity to plasminogen but it developed the inhibitor's properties of fibrinolytic activity. On the 16th enzyme therapy day, 8 hrs. after SK 500 000 e.u. i/v infusion, the patient had the anaphylactic shock and myocardial infarction due to the inhibition of streptokinase-induced fibrinolytic activation, hypercoagulaemia and hyperfibrinogenaemia.. The patient was transferred to the Intensive Care Unit, after that to the Cardiology Unit. SK was cancelled, but Actilyse (t-PA), due to socially-economic conditions, was not indicated.

In this case streptokinase was acting as the inhibitor of fibrinolysis. SK-induced hypercoagulaemia caused belated ( after 8 hrs.) anaphylactic shock and myocardial infarction. On the 13th day after myocardial infarction was diagnosed, hyperfibrinogenaemia and hypercoagulaemia did not show any regression (Table Nr.1). The danger for thrombembolic complications still persisted.

In a month after the treatment at the Cardiology Unit, due to dysfunctions of cerebral blood circulation and the left side hemiparesis, the patient got hospitalized in the Neurology Department. Two months' later, the patient had a repeated attack of myocardial infarction. Prostatitis and phlebothrombosis of the small pelvis were disregarded. In almost 2,5 months after the myocardial infarction, the complications of urogenital origin were manifested: urine retention as a result of the prostate edema and paraprostatitis, the inflammation of the urogenital venous plexus with hypercoagulaemia. Due to subjective and objective urogenital findings (residual urine 250-300 ml), the patient was repeatedly hospitalized in the Urology Department and received streptokinase i/v in the dosage of 3000-300 000 e.u. once a day for 25 days, in total 4 700 000 e.u. Antibiotics were not administered. Coagulogram indices normalized (Table Nr.1). Angina pectoris seizures disappeared. Family physician's supervision was indicated.

Conclusion:

1) Streptokinase may possess not only the potencies of plasminogen activator, but that of plasmin inhibitor-inactivator as well.

2) Chlamydial prostatitis, paraprostatitis, the inflammation of the urogenital venous plexus (phlebothrombosis of small pelvis) may be the cause of the inflammatory dyscoagulaemia, hypercoagulaemia, hyperfibrinogenaemia, thrombolytic complications, as well as myocardial infarction and dysfunction of cerebral blood circulation, therefore fibrinolytic enzyme system activators are indicated.

3) Streptokinase may show the properties of plasminogen activation inhibitor (inactivator) at a higher fibrinogen concentration in the blood.

4) In cases of phlebothrombosis of small pelvis, the pathogenetic therapy is indicated by using SK and heparin.

5) In cases of streptokinase-induced hyperfibrinogenaemia and hypercoagulaemia, one should indicate the tissue pasminogen activator (t-PA) extra with an aim to prevent the characteristic side-effects due to SK.

6) Streptokinase, losing its catalytic activity to plasminogen, or, by acquairing the properties of fibrinolytic activation inhibitor, may cause belated allergic or anaphylactic reactions, i.e. 6-8-10 hours after streptokinase i/v infusion. In such a case, streptokinase course must be interrupted.

In a certain time interval (3-6 months), a repeated enzyme therapy course with SK does not expose a danger to shock or some other anaphylactic reaction. SK has lost its plasminogen inactivator-inhibitor's properties during this time and even a relatively small enzyme doses can normalize the coagulogram indices.

In reinfections, when the enzyme therapy course with SK is repeated, the curative reaction of SK is felt in several months or even years (Table Nr.4).

Table 1